Peripheral Nerve Injections and Procedures for Chronic Pain

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be medically reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(1)(D) and (E) Items and services related to research and experimentation.

Title XVIII of the Social Security Act, §1862(a)(7) and (14) excludes routine physical evaluations and non-physicians services unless the services are furnished under arrangements.

Title XVIII of the Social Security Act, §1861(s)(2) Medical and Other Health Services

42 CFR §410.74 Physician assistants' services, §410.75 Nurse practitioners' services, §410.76 Clinical nurse specialists' services

42 CFR §419.22 Hospital services excluded from payment under the hospital outpatient prospective payment system

CMS Internet-Only Manual, Pub.100-03, Medicare National Coverage Determinations Manual, Chapter 1, Part 1, §30.3 Acupuncture.

CMS Internet-Only Manual, Pub.100-03, Medicare National Coverage Determinations Manual, Chapter 1, Part 2, §150.6 Vitamin B12 Injections to Strengthen Tendons, Ligaments, etc., of the Foot and §150.7 Prolotherapy, Joint Sclerotherapy, and Ligamentous Injections with Sclerosing Agents, and §160.7 Electrical Nerve Stimulators.

CMS Internet-Only Manual, Pub.100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.4 Reasonable and Necessary Provisions in LCDs.

Definitions

Acute pain- The temporal definition of pain persisting for up to 4 weeks after the onset of the pain.

Subacute Pain – The temporal definition of pain occurring during the 4 to 12-week time period.

Chronic pain- The temporal definition of pain persisting for greater than or equal to 12 weeks after the onset of the pain.

Peripheral nerve block (PNB)- injection of local anesthetic near specific nerves outside of the central nervous system (brain/spinal cord) to interrupt pain signals.

Peripheral nerve injection (PNI)- injection near specific nerves. When used for delivery of steroid rather than interruption of pain signal it is referred to as injection, although the terms are sometimes interchangeable as all PNBs are injections, even though not all injections are PNBs.

Peripheral nerve denervation- loss or interruption of nerve supplies to muscle, organ or tissue and can be used therapeutically to destroy nerves as a modality to treat chronic pain. Mechanisms can include radiofrequency ablation [RFA] (thermal denervation), neurotomy (cutting), chemical destruction (use of agent to damage nerve permanently), and cryoneurolysis.

Coverage Guidance

This LCD is arranged by type of injection or denervation, and the indications for which it may be considered with coverage criteria outlined in the section. The LCD focuses on therapeutic injections/blocks and percutaneous denervation (usually RFA or cryotherapy). Surgical neurotomy or cutting procedures are beyond the scope of this LCD. The Limitation Section below applies to coverage for all conditions unless it is specifically made in the coverage section for the condition.

The injection types are in the following order:

1. Median Nerve Injection(s)
2. Sympathetic block(s)- Stellate Ganglion Block and Lumbar Sympathetic Block(s)
3. Digital nerve block(s)
4. Ganglion Impar Block(s)
5. Genicular nerve block(s) (GNB)
6. Morton’s Neuroma Nerve Injection(s)
7. Occipital Nerve Block(s)
8. Posterior tibial nerve block(s)
9. Pudendal Nerve Block(s)
10. Suprascapular Nerve Block(s)
11. Trigeminal Neuralgia Nerve Block(s)
12. Thoracic Nerve Block(s)

Indications and Limitations of Coverage

1. A PNI involves the use of an anesthetic with or without corticosteroids, and does not include injections of biologics (e.g., platelet rich plasma, stem cells, amniotic fluid, dextrose, etc.) and/or any other injectates (e.g., vitamins, ozone, etc.).
2. During denervation procedures for patients with implanted electrical devices (i.e., spinal cord stimulation, peripheral nerve stimulation, cardiac devices, etc.) and intrathecal pump delivery devices, providers should follow manufacturer instructions and extra planning as indicated to ensure safety of the procedure.
3. Use of moderate or deep sedation, general anesthesia, and monitored anesthesia care (MAC) is usually unnecessary or rarely indicated for nerve injections and, therefore, not considered medically reasonable and necessary. Even in patients with a needle phobia and anxiety, typically oral anxiolytics suffice. In exceptional and unique cases, documentation must clearly establish the need for such sedation for the specific patient.¹
4. Repetitive, regular or scheduled therapeutic PNIs are not reasonable and necessary for long-term pain management unless coverage is specified within the LCD.
5. "Dry needling" of neuromas or peripheral nerves is not medically necessary and will be a non-covered procedure.
6. It is not routinely necessary to perform peripheral nerve procedures on the same day as other injections (e.g., epidural steroid, facet, or trigger point injections) for neuropathic or nociceptive pain. If performed, the medical necessity of each procedure must be clearly documented in the medical record.
7. A therapeutic PNI or denervation not listed as covered in the LCD is non-covered.
8. Ultrasound guidance is considered reasonable and necessary only when it is necessary to identify superficial and deeper nerves, prior to the PNI to enhance accuracy, safety, and visualize needle placement.
9. Fluoroscopic guidance may be reasonable and necessary when performing reasonable and necessary RFA of a peripheral nerve to enhance accuracy, safety, and visualize needle placement. Use of image guidance for non-covered injections is also considered not reasonable and necessary.
10. An informed consent with risks and benefits is reviewed and documented in the medical record, including awareness of the risks of nerve damage and worsening pain.
11. PNIs and procedures to treat widespread diffuse pain (i.e., fibromyalgia, myofascial pain, and chronic pain syndrome), or systemic polyneuropathies are investigational and, therefore, are not considered medically reasonable and necessary.
12. Electrical stimulation is not considered reasonable and necessary when performing PNI.²

Contraindications

PNIs are contraindicated when there is an allergy to local anesthetics, beneficiary refusal or an active infection at the injection site. Relative contraindications are: inability to cooperate, severe cognitive impairment, unstable psychiatric illness, psychological overlay to the chronic pain, or coagulopathies.

Provider Qualifications:

The Medicare Program Integrity Manual (PIM) states services will be considered medically reasonable and necessary only if performed by appropriately trained providers.

Patient safety and quality of care mandate that healthcare professionals who perform neural procedures are appropriately trained and/or credentialed by a formal residency/fellowship program and/or are certified by either an accredited and nationally recognized organization or by a post-graduate training course accredited by an established national accrediting body or accredited professional training program. If the practitioner works in a hospital facility at any time and/or is credentialed by a hospital for any procedure, the practitioner must be credentialed to perform the same procedure in the outpatient setting. At a minimum, training must cover and develop an understanding of anatomy and drug pharmacodynamics and kinetics, as well as proficiency in diagnosis and management of disease, the technical performance of the procedure, and utilization of the required associated imaging modalities.

In addition to the above requirements, non-physician providers, such as certified nurse anesthetists, with certain exceptions, may certify, order, and establish the plan of care as authorized by State law (See Sections 1861[s][2] and 1862[a][14] of Title XVIII of the Social Security Act; 42 CFR, Sections 410.74, 410.75, 410.76, and 419.22; 58 FR 18543, April 7, 2000). Each practitioner must provide only those services within the scope of practice for each state.

Background

Chronic pain is pain that is experienced most days or every day in the past 3 months.³ It is the most common reason adults seek medical care.⁴ Chronic pain is associated with decreased quality of life,^5,6 opioid misuse,⁷ increased anxiety and depression,⁸ and unmet mental health needs.⁹

In 2023, 24.3% of adults experienced chronic pain, and 8.5% of adults experienced high-impact chronic pain (or 34.9% of adults who had chronic pain). Chronic pain has a higher incidence in women, American Indian, Alaska Native adults, and those aged 65 and older.¹⁰

The prevalence of neuropathic pain may be as high as 7 to 8%, accounting for 20 to 25% of individuals with chronic pain.¹¹ Best-practice recommendations for the treatment of peripheral neuropathic pain suggest first-line options including serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine and venlafaxine), gabapentin, tricyclic antidepressants, topical lidocaine, and transcutaneous electrical nerve stimulation. Pregabalin, tramadol, and combination therapy (combining antidepressants with gabapentinoids) are recommended as second-line treatments. High-concentration capsaicin patches and botulinum toxin A (BTX-A) are also recommended as second-line treatments, specifically for focal peripheral neuropathic pain. Third-line treatment options include strong opioids, as a last resort, in the absence of alternatives. Additionally, psychotherapy, including cognitive behavioral therapy and mindfulness, is recommended as a second-line therapy in conjunction with other treatments.¹²

PNIs have been proposed as an additional option for the management of chronic pain, both for diagnostic and therapeutic purposes. A nerve block is a form of regional anesthesia that attempts to inhibit impulse transmission distally in a nerve terminal, thus terminating the pain signal perceived by the cortex. PNIs generally involve the injection of a LA with or without corticosteroids using various techniques. PNIs may also have a role in diagnosing and informing subsequent treatments, such as RFA or cryoneurolysis for chronic pain conditions.¹³ Denervation procedures aim to destroy a nerve to disrupt its ability to transmit pain signals and can be performed with heat (thermal) or cooled RFA. Effects can be long-lasting, but nerve regeneration is common. Cryoneurolysis uses extreme cold to freeze and disrupt nerve function, causing temporary nerve function loss. The purpose of this LCD is to provide the scope of indications that are supported as reasonable and necessary for the usage of therapeutic PNIs and peripheral nerve denervation procedures for chronic pain management in appropriate patients.

Literature Analysis

This summary of the evidence is formatted by the type of intervention and outcome classification (i.e., efficacy/effectiveness, undesirable effects, patient experience, physical performance, and health care utilization). The findings of published evidence syntheses (e.g., systematic reviews, evidence reports) are prioritized when applicable to specific key research questions. The literature analysis emphasizes the research designs most applicable to the key questions (e.g., randomized controlled trials (RCTs) for efficacy-related questions). Multiple publications from the same dataset are grouped together in the analysis regardless of study design. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach domains of study limitations (risk of bias), indirectness (applicability), imprecision, and inconsistency formed the basis of appraisal of the certainty of evidence for efficacy/effectiveness studies.

A. Median Nerve Injections

Coverage

Median nerve injections may be considered for the management of carpal tunnel syndrome (CTS) in patients with clinical symptoms and physical exam findings consistent with CTS.

Limitations

1. PNI using only LA for the treatment of CTS is not medically reasonable and necessary and therefore non-covered.
2. Denervation for CTS is not reasonable and necessary and therefore non-covered.
3. The use of PNI for chronic pain conditions of the wrist and hand, other than CTS, are non-covered.

Summary of Evidence

Efficacy/Effectiveness

Steroid Injection versus Placebo

Ashworth, et al. evaluated the benefits and harms of corticosteroids injected in or around the carpal tunnel for the treatment of CTS compared to no treatment or a placebo injection.¹⁴ The systematic review was conducted employing standard Cochrane methods applied to RCTs and quasi-randomized trials. A total of 14 trials with 994 participants/hands with CTS were included. Only 9 studies (639 participants/hands) had usable data quantitatively. In general, these studies were at low risk of bias (ROB) except for 1 high-risk study. The trials were conducted in hospital-based clinics across North America, Europe, Asia and the Middle East. The reviewers reported there is probably an improvement in symptoms measured at up to 3 months of follow-up, favoring local corticosteroid injections (standardized mean difference [SMD] -0.77, 95% confidence interval [CI] -0.94 to -0.59; 8 RCTs, 579 participants; moderate-certainty evidence). Symptom improvement up to 6 months was still evident (SMD -0.58, 95% CI -0.89 to -0.28; 4 RCTs, 234 participants/hands; moderate-certainty evidence). Measures of functional outcomes showed there is probably improvement up to 3 months favoring local corticosteroid injections (SMD -0.62, 95% CI -0.87 to -0.38; 7 RCTs, 499 participants; moderate-certainty evidence).

The durability of different dosages of corticosteroid injections for CTS was addressed in a 5-year extended observational follow-up publication that explored the long-term effects involving 100% of the participants in the original RCT.¹⁵ Compared with placebo, there was no significant difference in mean change in symptom severity score from baseline to 5 years for the 80 mg methylprednisolone group (0.14 [95%CI, −0.17 to 0.45]) or the 40 mg methylprednisolone group (0.12 [95%CI, −0.19 to 0.43]).

Steroid Injection versus Splinting

Karjalainen, et al. performed a Cochrane systematic review that evaluated splinting for CTS.¹⁶ Eight studies were included in the comparison of splinting with corticosteroid injections. Moderate-certainty evidence (downgraded once for ROB) indicated that corticosteroid injections may provide a small but clinically unimportant benefit in symptom response compared with splinting at short-term follow-up. Although the mean difference (MD) favored corticosteroid injection, the 95% confidence intervals (CIs) excluded clinically meaningful benefit for injections. The mean symptom severity score (measured by the Boston Carpal Tunnel Syndrome Questionnaire [BCTQ]) scale, from 1 to 5, higher is worse, minimal clinically important difference [MCID] value = 1 point) was 1.88 with corticosteroids and 0.28 points worse (95% CI 0.04 worse to 0.51 worse; 5 studies, 459 participants, I² = 63%) with splints. At long-term follow-up, the certainty of evidence was downgraded to low (due to the ROB and unexplained inconsistency), indicating that there may not be clinically important benefits between splinting and corticosteroid injections. The standardized mean difference (SMD) was 0.09 (95% CI -0.66 to 0.83, 3 studies, 437 participants, I² = 93%). This translates to 0.06 points worse (95% CI 0.42 better to 0.52 worse) symptom severity score in the BCTQ Symptom Severity Scale with splinting compared with corticosteroid injections.

Moderate-certainty evidence (downgraded once for ROB) indicates that splinting probably provides little or no benefit compared with corticosteroid injections at short-term follow-up for functional outcomes. The mean functional status score measured by the BCTQ Functional Status Scale (scale from 1 to 5, higher is worse, MCID value = 0.7 points) was 1.76 for those who received a corticosteroid injection, and 0.16 points worse (95% CI 0.04 better to 0.36 worse, 5 studies, 459 participants, I² = 44%) for those who were prescribed a splint. At long-term follow-up, the evidence was downgraded to very low (once for ROB, once for unexplained inconsistency and once for imprecision as the 95% CI overlapped with the MCID value). The mean functional status score was 1.91 for corticosteroid injection, and 0.33 points worse (95% CI 0.40 better to 1.06 worse, 2 studies, 329 participants, I² = 89%) for those who were prescribed a splint.

Moderate-certainty evidence (downgraded once for ROB) indicates that corticosteroid injection probably results in a higher rate of remission from nocturnal paresthesia both at short-term and long-term follow-up. At short-term follow-up, 19 of 47 participants (40%) in the splinting group and 37 of 52 participants (71%) in the corticosteroid group had improved, corresponding to a risk ratio (RR) of 0.57 (95% CI 0.39 to 0.84, 1 study, 99 participants). At long-term follow-up, 13 of 45 participants (29%) in the splinting group and 40 of 50 participants (80%) in the corticosteroid group had improved, corresponding to a RR of 0.36 (95% CI 0.22 to 0.58, 1 study, 95 participants).

Steroid Injection versus Surgery (>3 months)

In a Cochrane systematic review, Lusa, et al. concluded it is uncertain if clinical improvement or symptom relief differs between surgery and corticosteroid injection (very low certainty evidence).¹⁷ The RR for clinical improvement with surgery compared to steroid injection was 1.23 (95% CI 0.73 to 2.06; 3 studies, 187 participants). For symptoms, the standardized mean difference (SMD) was -0.60 (95% CI -1.88 to 0.69; 2 studies, 118 participants). This translates to 0.4 points better (95% CI from 1.3 better to 0.5 worse) on the BCTQ. Hand function or pain probably does not differ between surgery and corticosteroid injection (moderate-certainty evidence). For function, the SMD was -0.12 (95% CI -0.80 to 0.56; 2 studies, 191 participants) translating to 0.10 points better (95% CI 0.66 better to 0.46 worse) on the BCTQ Functional Status Scale with surgery. Pain (0 to 100 scale) was 8 points with corticosteroid injection and 6 points better (95% CI 10.45 better to 1.55 better; 1 study, 123 participants) with surgery.

A prospective observational study reported on 1,564 consecutive patients with CTS.¹⁸ The patients were treated with corticosteroid injection as primary treatment (n=824), and the remaining underwent surgical decompression. A survivorship analysis was conducted on the non-surgical cohort to determine the rate of re-intervention and found that at 1 year, 15%, and 5 years, 33% underwent surgical management. Three hundred seventy-two (45%) of subjects received a second injection. Female gender, positive nerve conduction studies at diagnosis, and diabetes were associated with a higher rate of re-intervention. The strength of this study was consecutive enrollment, clear inclusion criteria, and large numbers, while limitations include risk of selection bias, uncontrolled variables like splinting, and a mean age below the Medicare population.

Undesirable Effects

Ashworth, et al. systematically reviewed the clinical evidence describing the undesirable effects of corticosteroid injections compared to placebo.¹⁴ The reviewers found adverse events were uncommon (low-certainty evidence). One study reported 2/364 injections resulted in severe pain, which resolved over "several weeks", and 1/364 injections caused a "sympathetic reaction" with a cool, pale hand that completely resolved in 20 minutes. One study (111 participants) reported no serious adverse events, but 65% of local corticosteroid-injected and 16% of the placebo-injected participants experienced mild-to-moderate pain lasting less than 2 weeks. About 9% of participants experienced localized swelling lasting less than 2 weeks. Four trials (229 participants) reported that they experienced no adverse events in their studies. Three studies (220 participants) did not specifically report adverse events. No serious or unexpected adverse events were reported in a large RCT that compared corticosteroid injection with night splinting. A systematic review concluded there is uncertainty about the risk of adverse effects between surgery and corticosteroid injections (very low-certainty evidence).¹⁷ In a systematic review, Karjalainen, et al. reported the types of adverse effects in participants receiving corticosteroid injection for CTS were: skin changes (n = 4), hot flashes (n = 17), and short-lasting or long-lasting (over 3 days) pain (n = 53), vasovagal syncope (n = 1), short-lasting pain (n = 2) or small hematoma (n = 1), short-lasting pain after the injection (n = 3), and increase in blood glucose level that required increasing the dose of oral anti-diabetic drugs (n = 1).¹⁶ The certainty of evidence was downgraded to very low (once for ROB, once for imprecision, and once for inconsistency).

Health Care Utilization

Ashworth, et al. performed a systematic review that assessed the requirements for surgery in patients receiving localized corticosteroid injections or placebo.¹⁴ The reviewers concluded that localized corticosteroid injection probably slightly reduces the need for surgery at 1 year (RR 0.84, 95% CI 0.72 to 0.98; 1 RCT, 111 participants, moderate-certainty evidence).

An extension of an RCT¹⁹ showed the number of participants who underwent surgical treatment between the 1-year and 5-year follow-ups was 4 participants (10.8%) in the 80 mg methylprednisolone group, 4 participants (10.8%) in the 40 mg methylprednisolone group, and 2 participants (5.4%) in the placebo group.¹⁵ The mean (SD) time from injection to surgery was 180 (121) days in the 80 mg methylprednisolone group, 185 (125) days in the 40 mg methylprednisolone group, and 121 (88) days in the placebo group. Kaplan-Meier survival curves showed statistically significant differences in time to surgical treatment [log-rank test: 80 mg methylprednisolone vs placebo (P 0.002), 40 mg methylprednisolone vs placebo (P 0.02), methylprednisolone 80 mg vs 40 mg, P 0.37)].

A follow-up study to an RCT²⁰ reported outcomes at 12 and 24 months, including the number of patients undergoing CTS surgery, and healthcare utilization.²¹ By 24 months, a greater proportion of the corticosteroid injection group had been referred for (28% vs 20%) and undergone (22% vs 16%) CTS surgery compared with the night splint group.

Potential Effect Modifiers

A systematic review and meta-analysis (SR/MA) concluded that ultrasound‑guided injection yielded more favorable results than landmark‑guided injection for the BCTQ symptom severity scale [SMD= −0.43, 95% CI (−0.68,−0.19), P=0.0005] and BCTQ functional status scale [SMD= −0.50, 95% CI (−0.84,−0.15), P=0.005].²²

Clinical Guidelines and Positions of National and Specialty Organizations

The 2024 American Academy of Orthopaedic Surgeons (AAOS) evidence-based clinical practice guideline “Management of Carpal Tunnel Syndrome” summarized their recommendation, “Strong evidence suggests corticosteroid injection does not provide long-term improvement of carpal tunnel syndrome” (Quality of Evidence: High, Strength of Recommendation: Strong).²³

A 2014 consensus-based multidisciplinary treatment guideline on the treatment of CTS found strong evidence for effectiveness in favor of corticosteroid injection compared with placebo in the short term.²⁴ The following recommendations achieved consensus:

• Intermediate-acting corticosteroid injections (e.g., methylprednisolone, triamcinolone) should be used in the treatment of CTS.
• The number of corticosteroid injections should be restricted to a maximum of 3.
  • In case more injections are given, an interval of 2 to 3 months between these injections should be considered.

The posited recommendation, “Treatment with a corticosteroid injection can be performed with or without a local anesthetic” did not achieve consensus.

Analysis of Evidence/Rationale for Decision Making

There is moderate certainty evidence that local corticosteroid injections probably reduce pain symptom severity in the short-term (up to 6 months) and the effects are likely clinically relevant compared to placebo injections. Moderate-certainty evidence indicated that corticosteroid injections may provide a small but clinically unimportant benefit in symptom response compared with splinting at short-term follow-up and low certainty evidence of no difference in the long-term. Moderate-certainty evidence indicates that corticosteroid injection compared to splinting probably results in a higher rate of remission from nocturnal paresthesia both at short-term and long-term follow-up. Very low certainty evidence suggests it is unclear if there is a difference in clinical outcomes between corticosteroid injections and surgery. Low certainty evidence indicates adverse events are uncommon and, most always, not serious with corticosteroid injections for CTS. Low certainty evidence suggests that corticosteroid injections result in more favorable short-term satisfaction and health-related quality of life (HRQoL) than do placebo or splinting. Moderate certainty evidence indicates that steroid injections for CTS may reduce the need for surgery or extend the time to surgery compared to placebo, but not splinting. A clinical practice guideline strongly recommends that corticosteroid injection does not provide long-term improvement of CTS.

Corticosteroid injections may be considered reasonable and necessary for the short-term management of CTS for up to 3 injections involving the same median nerve, at intervals of no less than 2 months, when supported by a documented clinical indication and expected therapeutic benefit. Repeat injections should be individualized based on documented clinical response, including objective or patient-reported improvement, and ongoing need for treatment. The application of more than 3 injections involving the same median nerve is not supported by current evidence.

B. Sympathetic nerve blocks (SNB)

SNBs include stellate ganglion blocks (SGB) and lumbar sympathetic blocks (LSB). Blocking sympathetic nervous activity may be achieved by injection of an anesthetic directly into sympathetic neural structures such as the stellate ganglion or the lumbar sympathetic chain.

Complex regional pain syndrome (CRPS) is a chronic pain syndrome characterized by hyperalgesia and allodynia of a limb or limbs, not restricted to a specific nerve territory or dermatome. It may develop after trauma or surgery but may occur in the absence of these conditions as well.²⁵

Coverage

SGBs or LSBs may be covered for the management of CRPS if both A and B are met.

A. The diagnosis of CRPS demonstrates ALL the following:

1. 1. An established diagnosis of CRPS, as defined by the International Association for the Study of Pain (IASP)²⁶ AND
   2. Continuing pain, which is disproportionate to any inciting event AND
   3. At least 1 symptom in 3 of the 4 following categories:
      • Sensory: Reports of hyperalgesia and/or allodynia
      • Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
      • Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
      • Motor/Trophic: Reports of decreased range of motion (ROM) and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin), AND
   4. Must display at least 1 sign at the time of evaluation in 2 or more of the following categories:
      • Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
      • Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry
      • Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
      • Motor/Trophic: Evidence of decreased ROM and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) AND
   5. There is no other diagnosis that better explains the signs and symptoms AND
   6. A standardized assessment at baseline of CRPS Symptom Severity, including both pain intensity and functional impairment (i.e., CRPS Severity Score [CSS])²⁶ AND
   7. The patient has tried standard of care (SOC) treatment options without improvement, and the treating provider has determined no alternative treatment options remain AND
   8. The beneficiary is receiving treatment by an interdisciplinary or a multidisciplinary team addressing at a minimum the psychological effects and the functional impairments of CRPS.²⁶

B. Sympathetic nerve blocks

1. 1. For initial SNB to be considered medically reasonable and necessary, the patient must meet the diagnostic criteria for CRPS as defined in Section A above.
   2. For subsequent SNB, ALL the following conditions must be met:
      1. A diagnosis of CRPS according to the above criteria, AND
      2. A positive clinical response as documented by a significant reduction in pain of ≥50% immediately following the procedure AND
      3. Presence of sympathetic blockade AND
      4. SGB: Evidence of a successful injection, including temporary Horner’s Syndrome (droopy eyelid, constricted pupil, facial flushing, nasal congestion, and increased temperature in the arm/hand).
      5. LSB: either a temperature increase in the ipsilateral foot (≥ 2°C) or a temperature difference between both feet of ≥ 1.5°C at 20 minutes post-block.²⁶ AND
      6. The beneficiary continues to receive treatment by an interdisciplinary or a multidisciplinary team that addresses the psychological effects and the functional impairments of CRPS.

Frequency limitation:

When performing more than 5 blocks per beneficiary per lifetime,²⁷ documentation of continued sustained benefit of the block(s) as measured by a 5-point decrease in the CSS from baseline for 3 months or longer is required.

The use of sympathetic blocks for other chronic pain indications is not supported by sufficient evidence and is considered investigational.

Summary of Evidence

Systematic Reviews

Tian, et al. conducted a SR/MA comprised of 12 RCTs (n=422) to compare the efficacy of SGB therapy for CRPS related to pain duration of at least 6 months.²⁸ They reported a decrease in pain using the visual analog scale (VAS) (4 studies) and the numeric rating scale (NRS) (3 studies), a slight decrease in heart rate (1 study), and skin temperature (3 studies). Limitations included high heterogeneity, unclear allocation concealment in half of the included studies, a limited number of studies, and an overall high ROB. Larger sample sizes with more robust RCTs are needed to confirm the efficacy of SGB in the treatment of CRPS pain.

O’Connell, et al. conducted an updated Cochrane review of the previously published work in 2005 on local anesthetic sympathetic blockade (LASB) of the sympathetic chain to treat people with CRPS.²⁹ This review included 12 RCTs (N=461) that evaluated the effect of sympathetic blocks with LA as compared to placebo, no treatment, or alternative treatments in children or adults. The evidence was evaluated and downgraded due to limitations, inconsistency, imprecision, indirectness, or a combination, leaving the certainty of evidence to be low to very low. Due to the lack of high-quality evidence and paucity of literature, reviewers upheld the previous conclusion that there is not enough evidence to support or refute the use of sympathetic block for CRPS. With the scarcity of published literature, they are unable to conclude the efficacy or safety of sympathetic blockades. They further stated that the current data does not suggest that LASB is effective for pain reduction in CRPS.

Ferraro, et al. conducted a Cochrane review of systematic reviews.³⁰ The authors could not identify high-certainty evidence for the effectiveness of any therapy for CRPS. There was moderate-certainty evidence that lidocaine LASB probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine SGB, but no effect size was reported. They concluded that “until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult “. This was a well-conducted systematic review.

Frequency of stellate ganglion blocks

The optimal frequency and number of SNBs for the treatment of CRPS is unclear. Datta, et al. conducted a single-arm intervention with SGB in 287 patients with documented CRPS.²⁷ The authors found that most patients (57.1%) responded to 2 injections with moderate pain relief, while 4.1% had minimal pain relief even after > 3 injections. This study was judged to be low-certainty evidence given the study design, small sample size, and lack of generalizability to the Medicare population.

In the absence of clinical guidelines or high-/moderate-quality research evaluating the effectiveness, the optimal number and frequency of SNB for the treatment of CRPS, the National Medicare claims data from December 2015 to 2025 for HCPCS 64510 and 64520 were reviewed. Most beneficiaries (80%) underwent between 1 and 5 SNBs for the treatment of CRPS, aligning with Datta et al. findings.²⁷

Craniofacial Postherpetic Neuralgia

Wang, et al. performed an RCT of 36 subjects with craniofacial postherpetic neuralgia (PHN) comparing ultrasound (US)-guided SGB, extracorporeal shock wave therapy (ESWT), or both.³¹ VAS and Pain Disability Index (PDI) significantly decreased in all groups, with the largest decrease in the combined treatments. The authors concluded that US-guided SGB with shock wave therapy is safe and effective and may significantly improve the pain in PHN patients. Limitations included a lack of generalizability (single-site study), imprecision (due to small sample size), limited duration of follow-up, and methodological limitations, including uncertainties regarding randomization, allocation concealment, blinding approach, sample size calculation, and the lack of a control group, resulting in a high ROB.

Post-traumatic stress disorder (PTSD)

Rae Olmsted, et al. conducted a multisite, blinded, sham-procedure, RCT to determine if paired SGB treatments at 0 and 2 weeks would result in improvement in the mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores (TSSS) from baseline to 8 weeks in 113 subjects with PTSD. At 8 weeks, SGB subjects achieved a greater reduction in mean change in CAPS-5 TSSS as compared to sham (SMD, 0.56 [SD, 0.09; 95%CI, 0.38-0.73]).³² No serious adverse events were reported. Authors concluded that 2 SGB treatments 2 weeks apart reduced CAPS-5 TSSS over 8 weeks. Limitations included the short duration of follow-up, limited sample size, lack of blinding of the investigators and possibly the participants, and uncertainty about generalizability due to the strict inclusion criteria.

Undesirable Effects

Information about undesirable effects (i.e., complications, adverse events, side effects) was reported in 2 systematic reviews and 3 RCTs. A SR/MA comparing the efficacy of SGB therapy for CRPS-related pain.²⁸ The most common adverse events in 3/12 (25%) of the studies were reports of dizziness and headache.

There is an updated review of previously published work in 2005 on LASB of the sympathetic chain to treat people with CRPS, which found that 6 of the 12 studies reported minor adverse events.²⁹ Subjects who received US-guided SGB with shock wave therapy experienced adverse events that included skin bruising and slight swelling in 3 subjects.³¹ An RCT assessed the effect of US-guided stellate blocks with 3 volumes of 1% lidocaine (4, 6, and 8 ml) on the skin temperatures of the hand, axilla, and face. Adverse events included hoarseness (11.8–15.2%) and dysphagia (2.9–6.1%), with transient headache, somnolence, and xerostomia being reported more frequently in the 8 ml group (p = 0.034).³³ An RCT comparing SGB to a placebo block reported that 6 adverse events occurred, with no serious adverse events being reported.³²

Clinical Guidelines

Harden, et al. conducted a narrative review to establish practical guidelines for the diagnosis and management of CRPS.²⁶ The authors highlighted the challenges posed by the current “evidence vacuum” and the need to adhere to strict definitions of CRPS (IASP) and adopt standardized scales in clinical practice to evaluate treatment responses (CSS). They also recommended using a holistic approach of care, preferably in interdisciplinary settings to treat patients with CRPS²⁶, using SNB as an adjuvant treatment.

Analysis of Evidence/Rationale for Decision Making

As the mechanisms and pathophysiology of CRPS are multifactorial, this presents unique challenges to treatment due to the dynamic and varied/diverse nature of its clinical symptoms. While there are some positive trends for SNB, there is a lack of high-quality data, defined patient selection, and long-term outcome data for clinical application. CRPS is an orphan condition with no interventions proven effective in large-scale clinical trials.^26,29,30 Thus, the limited use of SNB in interdisciplinary clinical settings is supported when the diagnosis of CRPS has been clearly established, all other treatment modalities have been exhausted, and when patients have experienced meaningful improvement in clinical outcomes from the advanced interventions as recommended by clinical guidelines.²⁶ The application of more than 5 SNBs for the treatment of CRPS is not supported by current evidence nor by National Medicare claims data.

C. Digital Nerves

Background

Digital nerve blocks (DNBs) are commonly used to anesthetize the digit for acute and non-acute conditions. Blocks can be used in the finger web space, flexor surface blocks (transthecal and tumescent), great toe digit block, subcutaneous palmar digital nerve block, and other approaches.³⁴ Investigations have been done to explore the role of DNBs as therapeutic management for chronic pain from rheumatoid arthritis (RA).

Coverage

DNBs for chronic pain from RA or other etiologies are non-covered.

Summary of Evidence

Efficacy/Effectiveness Outcomes

Systematic Review & Meta-Analysis

Ito, et al. evaluated the efficacy of traditional (TD), transthecal (TT), and single subcutaneous (SC) palmar DNBs.³⁴ Time to onset of anesthesia, duration of anesthesia, incomplete anesthesia, and injection pain were considered. No significant differences between groups were reported for any outcome. ROB was evaluated as high (selection and reporting bias). Additionally, the study protocol was unclear, including the inclusion/exclusion criteria. Overall, this review was limited due to the inclusion of poor-quality studies and clinical heterogeneity in the anesthetics and dosage administered.

Randomized Control Trials (RCTs)

Elsaman, et al. evaluated the effectiveness of DNBs in 83 (mean age 38.8 years) subjects with RA; more specifically, bilateral proximal interphalangeal (PIP) arthritis.³⁵ DNBs were performed in the dominant hand in 50% of participants, while the other hand served as control. The treatment group received 0.5ml of bupivacaine hydrochloride 0.5%, while 0.5ml of saline 0.9% was used as a control in the group. At 2- and 8-weeks intervals, the active side showed significantly less clinical and US scores when compared to the control side. Limitations include a small sample size and short-term follow-up, which were not sufficient to determine the duration of remission if achieved by DNB. While preliminary results appear promising, the authors call for further research, including the number and size of joints, the technique, and dosing for block administration.

Undesirable Effects

In a systematic review, 2 studies evaluated undesirable effects. In the traditional DNB group, 6 complications were reported: infection in 2 cases (2.9%), sensory impairment in 3 (4.4%), and pain in 1 (1.5%). In the SC palmar group, there was 1 case of infection (1.5%), 2 reported sensory impairment (2.9%), and 3 reported pain (4.4%). Two individuals reported injection site pain at 24 hours in the TT DNB group (2/28; 7.1%). In the combined TT DNB plus single SC palmar DNB group, 3 individuals reported injection site pain (1/30; 3.3%).³⁴

A RCT reported on adverse events that included pain, tingling, and injection site bleeding. No significant differences were reported between groups.³⁵

Patient Experience

Two studies included in the systematic review evaluated patient satisfaction, reporting 81.48% of the patients preferred the SC route (P = 0.0014). Another study reported 33% selected the TD route, 25% of the subjects selected the SC route, and 43% selected the TT route. Subjects reported 33%, 25%and 43% satisfaction in TD, SC, and TT, respectively.³⁴

Potential Effect Modifiers

A RCT found that greater improvements were reported when the dominant hand was injected as compared to the nondominant hand; although at 8 weeks a nonsignificant difference was reported in treatment effect.³⁵

Analysis of Evidence/Rationale for Decision Making

Aside from a single small RCT, the available literature on DNBs for the management of chronic pain from RA or other etiologies was primarily comprised of case reports and literature reviews that lacked the high-quality studies necessary to establish efficacy and safety. In the absence of adequate evidence of clinical benefit, the statutory standard for reasonable and necessary care under §1862(a)(1)(A) is not met.

D. Ganglion Impar Blocks

Background

The ganglion impar is located on the anterior surface of the sacrum, and nerve blocks can impact the lower pelvis, perineum, and coccyx. Coccydynia is pain at the coccyx or lowest region of the vertebral spine. Chronic pain from coccydynia is uncommon.

Coverage

Therapeutic ganglion impar block (GIB) and denervation procedures are considered investigational and therefore are non-covered.

Summary of Evidence

Efficacy/Effectiveness

Systematic reviews

Andersen, et al. systematically reviewed 8 studies (1 RCT, 1 retrospective cohort, and 6 case series), finding that RFA achieved clinically superior pre/post differences in pain intensity compared to GIB at a mean of 5.54 months following intervention.³⁶ In contrast, Choudhary, et al. reported data from 7 non-randomized studies of an intervention (NRSI).³⁷ The between-group differences showed a clinically significant difference in the short term (3-4 weeks), favoring GIB over other treatment modalities reported, including coccygectomy, rhizotomy, conservative care/ physical manipulation, and others. There was no significant difference in pain status between GIB and RFA in the long term (6 months).

There were substantial limitations for both reviews. Almost all the studies included were observational, which confounded judgments about efficacy. All the studies had small sample sizes, resulting in imprecision. Comparisons were largely based on samples from different populations, all of which had mean ages well below those of most Medicare beneficiaries (very serious indirectness). There was very serious heterogeneity across studies in terms of the participants, intervention, and duration of follow-up. Additionally, 1 review used an unvalidated ROB appraisal tool that employed a checklist approach with an unweighted scoring scheme.³⁶

Mazzoleni, et al. conducted a systematic review of clinical trials investigating coccygodynia’s therapeutic options.³⁸ The authors found 6 RCTs examining the effectiveness of GIB for the treatment of non-cancer-related coccygodynia. GIB had favorable effect; however, the studies had small sample sizes, variable follow-up durations, and heterogeneity among study designs. The authors concluded that further research and high-quality RCTs are needed to establish standardized guidelines and management protocols for coccygodynia management. The protocol of this systematic review was not registered, the span of the search strategy was not reported, it included non-randomized studies, and publication bias was not addressed. The quality of this SR using the AMSTAR 2 tool³⁹ was rated as low.

Jevotovsky, et al. included in a systematic review of 17 studies with 625 coccydynia patients treated with GIB.⁴⁰ All studies reported some level of improvement in pain. The meta-analysis included 11 studies totaling 391 patients with a baseline pain score of 7.93 (95% CI 7.81 to 8.04). GIBs were effective in reducing coccygeal pain at short-term (up to 3 months), intermediate-term (3–6 months), and long-term (greater than 6 months) follow-up. SMDs were −2.73 (95% CI −3.45 to −2.01), −2.13 (95% CI −2.82 to −1.45), and −1.86 (95% CI −2.58 to −1.15) at 3 months, 3–6 months, and >6 months, respectively.

The GRADE assessment rated the certainty of evidence as very low, reflecting unexplained heterogeneity and limited high-quality trials. There were significant deviations from the registered PROSPERO protocol. The interventions meant to be studied were the following: GIB, presacral block, RFA, pulse radiofrequency, and ganglion impar injection; however, the authors only reported on GIB. The authors also included non-randomized studies, generating precise estimates of intervention effects that may be inaccurate because of residual biases. The authors also failed to report on the sources of funding for the studies included in the review, and publication bias was not addressed. The quality of the systematic review was low.³⁹

Randomized Controlled Trials

A single RCT, which was not included in either systematic review, concluded there were clinically significant differences in pain from 1 month through all follow-up periods, including 12 months post-procedure, favoring RFA compared to GIB.⁴¹ Qualitative limitations included some concerns about ROB (uncertainty about allocation concealment and loss to follow-up), imprecision, indirectness, and the analysis was limited primarily to descriptive statistics.

Observational studies

There were 2 NRSI that compared GIB with RFA for patients diagnosed with chronic coccydynia.^42,43 Improvements in pain intensity were similar in both groups for up to 3 months after the procedure. RFA produced clinically superior benefits for pain outcomes measured beyond 3 months for up to 1 year. Both studies were limited by their retrospective observational design, imprecision, and indirectness.

Le Clerc, et al. conducted a retrospective analysis of a single center of 83 participants where blocks were performed for the clinical indication of moderate to severe chronic refractory pelvic and perineal pain with CT guidance.⁴⁴ A total of 220 GIBs were performed in 83 patients; 193 (87.7%) of these 220 procedures were positive with an immediate but transient reduction of pain by more than 50%, including complete but always transient pain relief during the hour following the procedure in 119 (54.1%) procedures. This observational study had a short-term follow-up. Twenty-one patients did not complete the 3rd block, representing an attrition rate of 25%. The percentage of patients reporting worse symptoms was 8.4% and 50.6% reported no long-term change. Although the authors concluded that repeated GIBs allowed short-term reduction of pain intensity with a moderate intermediate-term effect, there is currently low certainty evidence that these blocks are effective in the long term in treating chronic nonmalignant pelvic pain from many etiologies.

GIB versus Coccygeal Nerve Block (CNB)

One RCT compared the efficacy of GIB and CNB in treating chronic coccydynia.^45,46 No significant difference was observed in the pain and functional outcomes at 4 and 12 weeks after treatment. This study was rated as having a high ROB, imprecision, and indirectness. Additionally, aside from P-values, the analysis was limited to descriptive statistics. This restricted the ability to assess the variability of effects and to control for confounding.

GIB versus Caudal Epidural Injection

A small retrospective cohort study compared the observed difference on pain outcomes for patients treated with manipulation and either GIB or a caudal epidural injection.⁴⁶ There were no differences between groups at 10 days post-procedure. GIB produced clinically superior pain intensity improvement at 1, 3, and 6 months. At 6 months follow-up, painless sitting time was significantly greater in the GIB group (P < 0.0001). The main limitations of the study were its retrospective, uncontrolled design, imprecision, and indirectness.

GIB versus Other Interventions

Andersen, et al. systematically reviewed the effectiveness of GIB compared to a range of interventions for patients having chronic coccydynia.³⁶ Coccygectomy, extracorporeal shockwave therapy, and corticosteroid injection demonstrated clinically superior pre/post differences in pain intensity compared to GIB at a mean follow-up period of 5.54 months. Improvement in pain intensity favored GIB over usual conservative care, which may be clinically relevant, and stretching/manipulation, which was not clinically significant. Limitations included the types of study designs reviewed (7 of 8 studies were observational designs, 6 were non-comparative), imprecision, indirectness, and inconsistency.

Undesirable Effects

The reporting of undesirable effects (i.e., complications, adverse events, side effects) was assessed in 1 systematic review, 3 RCTs, and 2 NRSI.^41,43,45-47 Overall, the reported complications were few, with no serious adverse events observed in any patient.

Analysis of Evidence/Rationale for Decision Making

The certainty of evidence was judged to be very low due to a high ROB, imprecision, indirectness, and inconsistency. It is very uncertain whether GIBs have a benefit in the treatment of chronic coccydynia and perineal pain. Therefore, they are considered investigational.

E. Genicular Nerve Injections and Procedures

Background

PNIs consist of injections of local anesthetics, with or without adjuvant steroids, into the perineural region of the superior medial, superior lateral, and inferior medial genicular nerves and may include the terminal articular branch of the common fibular nerve, inferior lateral genicular nerve, recurrent fibular nerve, nerve to vastus medialis, nerve to vastus lateralis, nerve to vastus intermedius, and the infrapatellar branch of the saphenous nerve.^48,49

There are 2 different types of genicular nerve ablations: continuous (thermal, conventional and cooled) and pulsed radiofrequency (PRF).⁵⁰ Conventional genicular nerve ablation causes nerve structural alterations beginning at 45^° C and complete denaturation of neural tissue at 80° C.⁵¹ The cooled ablations use internally cooled probes (approx. 60° C) to potentially create larger nerve lesions. The pulsed ablations use lower temperature with an alternation of repeating high-frequency pulses rather than continuous heat, potentially reducing tissue damage compared to other thermal methods.

Definitions

Radiofrequency ablation (RFA)- probes deliver high-frequency electric current to transfer targeted thermal energy to nearby neural tissue, thus resulting in tissue destruction and Wallerian degeneration of the surrounding nerves.^52-54

Pulsed RFA- delivers repeated bursts of lower temperature radiofrequency-generated heat to tissues, resulting in non-ablative nerve disruption primarily at the cellular level, while minimizing damage to the surrounding tissues.^55-57

Continuous RFA- an electrode which produces radiofrequency energy, causing oscillation of the ions in surrounding tissues, results in friction and generates heat, resulting in thermal destruction of the nerves.⁵³

Cooled RFA- circulates cooled water through the probe tip, allowing it to maintain a lower temperature at the tip-tissue interface

Conservative treatment- for knee osteoarthritis (KOA) includes multimodal interventions such as exercise (e.g., physical therapy [PT], home exercises, aquatic therapy, etc.), weight loss, biomechanical interventions (e.g., knee braces, knee sleeves, foot orthoses), oral pharmacotherapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], SSRIs), and intra-articular injections [IAIs] (e.g., corticosteroids, hyaluronic acid [HA]).⁵⁸

Coverage

A. Diagnostic genicular nerve injections (GNI)

Diagnostic GNI may be administered as part of the evaluation for a denervation procedure for the treatment of chronic osteoarthritis knee pain when ALL of the following criteria have been met⁶⁰:

1. 1. Moderate to severe osteoarthritis (OA) that causes associated pain, decreased function, limited mobility, and disability objectively measured on a pain or disability scale* AND

   2. Pain that has been present for a minimum of 3 months with documented failure to respond to noninvasive conservative care management (as tolerated) ⁶⁰ AND

   3. Radiographic confirmation of KOA Grade 3-4 Kellgren-Lawrence (KL) grading^61-63

*Pain assessment must be performed and documented at baseline, after each diagnostic procedure, using the same pain scale for each assessment. A disability scale must also be obtained at baseline to be used for functional assessment (i.e., if the patient qualifies for treatment).

The scales used to measure pain and/or disability must be documented in the medical record. Acceptable scales include but are not limited to: Verbal Rating Scales, Numerical Rating Scale (NRS), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Intermittent and Constant OA Pain (ICOAP), and those that assess function such as Knee Injury and Osteoarthritis Outcome Score (KOOS), Lequesne index, or Dynamic Weight-bearing Assessment of Pain (DAP).

Limitations

1. Intra-articular knee injections (IAIs) within the past 3 months.
2. Recent knee surgery within the past 3 months.
3. Presence of inflammatory knee arthropathy, including RA, gouty arthritis, or other systemic inflammatory diseases.
4. Injections of biological or other substances not FDA-designated for this use.
5. Use of high volume of injectant because low volumes (e.g., 0.3–0.5 ml) at the relevant target nerve locations is required to enhance the prognostic accuracy for subsequent and potential genicular RFA^48,64

Frequency Limitation: For each covered knee, no more than 2 diagnostic joint sessions will be reimbursed in recognition that the pain generator cannot always be identified with the initial diagnostic procedure.

B. Genicular nerve ablation (GNA)

Genicular Nerve Ablation (RFA or cryoneurolysis⁶⁵) may be considered when all criteria for diagnostic block is met⁶⁴:

1. 1. There is a positive response of ≥50% improvement in pain, consistent pain relief or function for at least 3 months after a diagnostic GNI⁶⁶
   2. The patient is a poor surgical candidate or declines surgical intervention as documented in the medical record.

Limitations

1. GNA for chronic knee pain after a total knee replacement beyond the perioperative period is non-covered.⁶⁷
2. Cryotreatment with temperatures around -88 degrees Celsius are not medically reasonable and necessary outside the perioperative setting.^65,69

Frequency Limitation: For each knee, no more than 2 radiofrequency sessions will be reimbursed per rolling 12 months.⁶⁸

C. Therapeutic Genicular Nerve Injections

1. There is insufficient evidence to support use of therapeutic GNIs.^68,70

Summary of Evidence

Efficacy/Effectiveness

Systematic Reviews

Two SR/MAs were identified as representative of the body of evidence for GNI.^68,70 Both evidence syntheses were published in 2025 and were critically appraised as high-quality reviews, using the validated AMSTAR-2 tool.³⁹

Almeida, et al. assessed the efficacy and safety of minimally invasive interventions targeting the genicular nerves in KOA.⁶⁸ This meta-analysis included 8 RCTs (N = 518) that compared GNB to placebo/sham, IAIs, physical therapies, alcoholic neurolysis, and RFA. The results show evidence for GNB versus sham (saline) is very uncertain based on a single study suggesting small improvements in pain and function at 4 weeks (downgraded for ROB, imprecision, and inconsistency). For GNI vs IAI, the evidence is very uncertain based on 1 single study suggesting small improvements in pain and large improvements in function, favoring GNB at 4 weeks (downgraded for ROB and imprecision). The evidence suggests that GNB may result in a very small reduction in pain compared to physical therapies in 4 weeks (MD −0.66, 95% CI −0.99 to −0.34, 3 trials), and at 12 weeks (MD −0.56, 95% CI −0.84 to −0.28, 3 trials), with minimal improvement in function (downgraded for ROB and imprecision). The evidence is very uncertain based on a single study suggesting no difference in pain or function at 4 weeks, with alcoholic neurolysis showing better outcomes at 24 weeks (downgraded for ROB, imprecision, and inconsistency).

The reviewers concluded that the use of related minimally invasive interventions (e.g., GNB) for KOA is currently not supported by high-quality evidence. The overall benefits across outcomes were inconsistent and minimal. There is great uncertainty about their effects in the long-term, as the available evidence is limited. The very low certainty ratings across all comparisons indicate substantial uncertainty about the true effectiveness of GNB. As a result, any observed effects may not translate into meaningful clinical benefits for patients, and the therapeutic use of GNB should be approached with caution until more robust evidence is available.

Li, et al. employed meta-analysis in a systematic review that explored the effect of GNB on various causes of knee pain (e.g., RA, juvenile idiopathic arthritis, perioperative knee pain, OA).⁷⁰ The main analysis, which comprised 13 RCTs (N=731), did not permit the assessment of the discrete effects of GNB in patients diagnosed with KOA. A subgroup analysis that singled out participants with KOA, found pain scores were not statistically different from active comparator interventions (intra-articular corticosteroid injection [IACSI], PT, alcoholic neurolysis) at 2 weeks [SMD = −1.29, 95% CI (−3.15, 0.57)], 1 month [SMD = −0.86, 95% CI (−1.79, 0.07)], and 3 months [SMD = −0.65, 95% CI (−1.32, 0.03)].

Two additional systematic reviews were identified, but they were not included in the analysis.^71,72 In both reviews, the analysis was limited to pre/post-within-group comparisons. Consequently, the efficacy/effectiveness findings were not informative.

Randomized Controlled Trials (RCTs)

Three RCTs were identified that evaluated efficacy/effectiveness outcomes and were not included in either systematic review.^73-75

GNB versus RFA

Ghai, et al. randomly allocated 32 participants to receive either a GNB using local anesthetic and steroid (GNB-LAS) or US-guided pulsed radiofrequency ablation (PRFA) of the genicular nerve.⁷³ Participants (mean age 59 years) had chronic (>3 mos.) moderate pain due to KOA (KL grade >2) and had not responded to 12 weeks of conservative therapy. There were multiple exclusion criteria, including prior knee surgery, uncontrolled hypertension (HTN) and diabetes, connective tissue disorders, neurological or psychiatric disorders, patients receiving IA knee injection with steroid or hyaluronic acid (HA) within 3 months, and those with a history of bleeding disorder. Pain scores decreased significantly (P < 0.001) in both the groups at 12 weeks and other follow-up times compared to baseline. At 12 weeks, no difference was found in the pain scores between the 2 groups (P = 0.724). Seventy-three percent of patients in the PRFA group and 66% in the GNB-LAS group achieved effective pain relief (≥ 50% pain reduction) in 12 weeks (P > 0.999). There was statistically significant (P < 0.001) improvement in functional WOMAC scores in both groups at all follow-up times. However, there was no intergroup difference in functional scores (P = 0.983).

This study had a low ROB. Small sample size (imprecision), uncertain applicability to the Medicare population (indirectness) due to the numerous exclusion criteria and single study site, short-term follow-up, and reduced power in the treatment success analysis relative to the analysis on the original continuous scale were the main limitations of this study.

GNB versus Conventional Pharmaceutical Treatment

Rathore, et al. enrolled 60 participants (mean age 59.1 years) with neuropathic knee pain fulfilling the American College of Rheumatology criteria for OA.⁷⁴ Potential participants were excluded if there was a history of recent knee trauma, prior knee surgery, steroid or hyaluronic knee injection in the previous 3 months, anticoagulant medication use, bleeding disorders, any psychiatric disorder, connective tissue disorder, drug hypersensitivity reaction, or any other comorbidity that could interfere with the outcomes. The study was conducted at a single location. The study compared the clinical effects of GNB plus supervised exercise with conservative management (i.e., paracetamol 1g twice a day and pregabalin 75 mg once per day) plus supervised exercise. Both groups improved from baseline at 2 and 4 weeks regarding neuropathic pain symptoms, using the PainDETECT scale. The GNB group showed a larger improvement; however, neither statistical nor clinical significance was reported. Pain intensity and functional outcomes showed statistically and clinically significant differences between groups, favoring GNB, at 2 and 4 weeks. This study was judged to have a high ROB due to very serious methodologic shortcomings (uncertainty about allocation concealment and the effect of lack of blinding on patient-reported outcomes). Additional limitations included imprecision (associated with the small sample size), no control group, indirectness (single setting and numerous exclusion criteria), and short-term analysis. The certainty of evidence was rated as very low.

Undesirable Effects

Information about undesirable effects (i.e., complication(s), adverse events, side effects) were reported in 2 systematic reviews,^68,72 9 RCTs,^{73,74, 76-82} and 2 non-comparative NRSI.^83,84 Overall, there were no significant safety concerns (e.g., swelling, motor weakness, sensory deficit, deafferentation pain) reported by any of the studies. Post-procedural complications were infrequent, transient, and minor (e.g., local pain, bruising, hypoesthesia, and edema). No adverse events were reported at follow-up assessments beyond 2 weeks. Patients typically resumed their normal activities after the procedure.

Genicular Radiofrequency Ablation

Systematic Reviews

Almeida, et al. systematically assessed the efficacy and safety of minimally invasive interventions targeting the genicular nerves in KOA.⁶⁸ This meta-analysis included 17 RCTs (N = 1,463) that compared RFA to usual care, placebo/sham, IAI therapies (e.g., corticosteroid, platelet-rich plasma [PRP], HA), physical therapies, alcoholic neurolysis, and GNB. The reviewers found very low certainty evidence suggests that RFA may result in moderate pain reduction at 4 weeks (MD −1.70, 95% CI −3.03 to −0.36) and at 12 weeks (MD −1.86, 95% CI −2.82 to −0.89) based on 6 trials (downgraded for ROB, imprecision and inconsistency). However, there is little to no difference in pain between 24 and 48 weeks, based on 3 trials and 1 trial, respectively. There were no significant improvements in function observed at any time point.

In comparison to other treatments, the reviewers found very low certainty evidence suggests that RFA may lead to small to moderate improvements in pain and function as compared to GNB up to 24 weeks based on a single trial (downgraded for ROB, imprecision, and inconsistency). There was very low certainty evidence that shows no significant difference between RFA and alcoholic neurolysis in pain or function at 4 and 12 weeks, based on a single trial (downgraded for ROB, imprecision, and inconsistency). There was very low certainty evidence that suggests RFA may result in moderate improvements in pain and function across multiple time points (pain 4 weeks MD −0.66, 95% CI −0.99 to −0.34, 4 trials; 12 weeks MD −0.61, 95% CI −0.82, −0.39, 5 trials, 24 weeks MD −1.83, 95% CI −3.06 to −0.60, 4 trials; 48 weeks MD −2.70, 95% CI −3.26 to −2.14, 1 trial) (downgraded for ROB, imprecision and incon­sistency). The evidence is very uncertain about the effect of RFA compared to usual care, based on a single study suggesting small to medium effect sizes for pain and function favoring RFA up to 24 weeks (downgraded for ROB, imprecision, and inconsistency). The evidence is very uncertain based on a single study suggesting moderate effect sizes for pain and function favoring RFA plus IA therapy (downgraded for ROB, imprecision, and inconsistency). The evidence is very uncertain based on a single study suggesting small to large improvements in pain and function, favoring RFA plus stretching (downgraded for ROB, imprecision, and inconsistency).

Chen, et al. employed a SR/MA approach in evaluating the short-term and long-term efficacy of RFA and explored the role of diagnostic GNBs in predicting treatment outcomes⁸⁵ The review encompassed 9 RCTs, totaling 714 patients (mean age range 57-69 years) diagnosed with chronic KOA (KL grades 2-4) who had failed conservative treatment. Percutaneous interventions included traditional genicular RFA (4 studies), cooled RFA (2 studies), and RF thermocoagulation (3 studies). Comparators included sham RFA, oral analgesics, and different types of IAIs. Five RCTs (N=490) provided data on pain scores at 6 months. The RFA group experienced statistically and clinically significant greater pain reduction compared to the control groups (weighted mean difference [WMD]: − 2.69; 95% CI: − 3.99, − 1.40; I² 97%). At 12 months, data from 4 RCTs (N=344) showed the between-group results were not statistically or clinically significant for pain (WMD: -0.88; 95% CI: -2.36, 0.61; I² 97%). Three RCTs reported clinically nonsignificant results for functional outcomes⁸⁶ at 6 months (WMD: − 4.40; 95% CI: − 7.12, − 1.68; I² 98%). Two RCTs (N=191) reported data on WOMAC in 12 months. The results were not statistically or clinically significant (WMD: 0.03; 95% CI: -0.25, 0.32; I² 100%).

A subgroup analysis categorized the studies into 2 groups based on whether a diagnostic GNB test was or was not conducted. The group having a positive result from the diagnostic GNB test consisted of 3 studies, which yielded a non-clinically significant result for pain at 6 months (WMD: -1.06; 95% CI: −1.96, −0.15). On the other hand, the non-diagnostic GNB group comprised 2 studies, which resulted in clinically but not statistically significant findings (WMD: -6.53; 95% CI: −15.03, 1.98).

There were significant limitations in this systematic review. First, the number of studies and total participants applied to each outcome was small. This was even more of a concern with the subgroup analysis. Second, the quality of evidence for most of the findings was judged to range from low to moderate. However, the appraisal did not include imprecision, which was present for the main outcomes (pain and function at 6 months). Additionally, there was significant unexplained heterogeneity for all outcomes when data was pooled from at least 2 RCTs. Based on the notes in the GRADE profile and the ROB 2 figure, all outcomes should have been downgraded due to study limitations (high ROB) (i.e., selection bias, performance bias, and detection bias). The overall certainty of evidence appears to be “very low” for each outcome.

Fogarty, et al. performed a systematic review to determine the effectiveness of fluoroscopically guided genicular nerve RFA for painful KOA.⁶² A total of 9 RCTs (2 with multiple publications) and 1 noncomparative NRSI (N=4) were included in the analysis. Patients (N=485) with chronic knee pain and KL grades 2-4 were included. Interventions assessed were any type of fluoroscopically guided genicular RFA technology (e.g., monopolar, bipolar, cooled). Comparators were sham, placebo, other active interventions, or no treatment. The primary outcome ‘treatment success was defined as >50% pain relief.’ Additionally, functional outcomes were reported. Six-month success rates for 50% or greater pain relief after RFA ranged from 49% to 74%. Compared with IA steroid injection, the probability of success was 4.5 times higher for RFA (relative risk [RR] = 4.58 [95% CI = 2.61–8.04]). When RFA was compared with HA injection, the probability of treatment success was 1.8 times higher (RR = 1.88, 95% CI = 1.38–2.57). The group mean functional scores improved in participants receiving genicular RFA compared to IA steroid and HA injections. There were serious limitations associated with this systematic review. All the relevant studies had a high ROB assessment. A meta-analysis could not be performed because of the heterogeneity of the available data. Results were based on data from single trials for each outcome. Between-group differences in change scores were not reported.

Randomized Controlled Trials (RCTs)

A single RCT was identified that evaluated efficacy outcomes and was not included in either systematic review.⁷³ This trial compared RFA with GNB and was summarized in the previous section.

Genicular Cryoneurolysis

Genicular cryoneurolysis (also referred to as cryoablation or cryoanalgesia of the genicular nerves) is a minimally invasive, image‑guided pain management procedure that applies extreme cold to targeted sensory genicular nerves supplying the knee joint to temporarily interrupt pain signal transmission. The procedure uses a percutaneous cryoprobe to create a localized ice ball around the nerve, producing reversible axonal injury (Wallerian degeneration) while preserving the nerve’s connective tissue structure, allowing for eventual nerve regeneration.⁸⁷

A randomized, assessor-blinded study of 80 subjects with KOA and KL grade 3 or 4 received cryoneurolysis (n=40) or cooled-RFA (n=40) and were followed for 24 weeks using NRS.⁸⁸ The authors concluded non-inferiority of cryoneurolysis compared to cooled-RFA. This study was limited by a small sample size, but did meet proposed target enrollment, short term follow-up and blinding.

Radnovich, et al. conducted a double-blind, sham-controlled, multicenter (USA) RCT to evaluate the efficacy and safety/tolerability of cryoneurolysis (using temperatures around -88 degrees Celsius) for reducing pain and symptoms in patients with mild-to-moderate KOA.⁶⁵ A total of 180 patients were enrolled and constituted the intent-to-treat (ITT) population. Participants (mean age = 60.8 years, 66% female, K-L grade 2/3, and responsive to a diagnostic block) were randomized 2:1 to cryoneurolysis (n=121) targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment (n=59). All randomized patients received their assigned treatment. The primary endpoint was the change from baseline to Day 30 in the WOMAC pain score adjusted by the baseline score and site. Secondary endpoints, including VAS pain score and total WOMAC score, were assessed in a pre-defined order. All patients were followed every 30 days through Day 120 post-treatment. Patients who demonstrated a durable benefit from treatment, as defined by a Day 120 WOMAC pain subscale score less than their respective baseline scores, were followed to Day 150, and those with a durable response at Day 150 were followed to Day 180.

The cryoneurolysis treatment group had a statistically significant greater WOMAC change from baseline to Day 30 (primary endpoint) than the sham treatment group. The MD between groups in WOMAC pain subscale score at Day 30 was 7.12 (95% CI 11.01 to 3.32, P = 0.0004). The point estimate difference was potentially clinically significant; however, effects ranged from trivial to clinically relevant.⁸⁹ Among patients who continued to have a benefit at days 120 and 150, respectively, those who received cryoneurolysis had statistically significantly lower WOMAC pain scores at Day 150 but not Day 180 than those who received sham treatment. The clinical significance of these results was uncertain. The cryoneurolysis treatment group had a statistically significant greater proportion of WOMAC pain responders (≥30% reduction from baseline) at Day 30 (P = 0.0015), and a nonsignificant trend towards a greater proportion of WOMAC responders on Day 60 (P =0.0430) and Day 90 (P = 0.0285), compared to the sham group; the responder rate was not statistically significant. Total WOMAC scores were statistically significant in favor of the cryoneurolysis group at Day 30.The range of results included clinically relevant between-group differences at these time points, as well as on Day 120.

The MD of the cryoneurolysis versus the sham group for the VAS pain score was statistically significant at Day 30 (P = 0.0073) but not at Day 60, 90, or 120. Among patients eligible for follow-up past Day 120, those in the cryoneurolysis treatment group had a statistically significant MD in VAS score at Day 150 compared to sham-treated patients. However, the VAS between-group differences did not achieve clinical significance at any time point.⁸⁶ A statistically significant greater proportion of patients in the cryoneurolysis group were VAS responders (≥30% reduction from baseline) at Day 30 (P = 0.0124) compared to the sham group; there were no statistically significant differences in response rates between the groups at Day 60 (P = 0.180), Day 90 (P = 0.400), and Day 120 (P = 0.5060).

There were no statistically significant HRQoL differences between groups on the SF-36 or in the proportion of perceived global impression of change (PGIC) responders at any follow-up assessment. The authors did not find any statistically significant differences in pain severity or function scores (WOMAC) at days 90 or 150.

This study was judged to have a low to moderate ROB. The primary limitations were industry sponsored study, patients began to more accurately guess their treatment group assignment based on their response to treatment over time, and participants in both arms experienced pain relief after the intervention at days 30, 60, 90 and 120, highlighting the effect of placebo. The primary outcome was met only in the short term (day 30).

This may have affected patient-reported outcomes, biasing results in favor of active intervention, and imprecise results for the primary outcome. Additionally, the authors used a low threshold (≥30%) for categorizing ‘responders’, which inflated the reported outcomes.

Nygaard, et al. in a double-blind RCT, investigated the effect of cryoneurolysis compared to sham in reducing pain intensity in patients with chronic KOA (K-L grade 2-4).⁶³ A total of 87 participants (mean age = 65.4), who experienced self-rated pain (>4/10) for more than 6 months and reported a reduction in knee pain intensity of 50% or more following a diagnostic GNB, were included in the study. Before US-guided cryoneurolysis, transcutaneous electrical nerve stimulation and anatomic landmarks were used for nerve identification. The IPBSN and the anterior femoral cutaneous nerve (AFCN) were targeted. Following either cryoneurolysis or sham intervention, both groups participated in an 8-week structured education and exercise program (GLA:D). Patients, therapists, and data managers were blinded, while the surgeon was not. The primary outcome was the difference in average pain at 14 days post-intervention between the cryoneurolysis and sham groups. Secondarily, safety and efficacy (pain and function) exploratory outcomes were assessed after 6 and 12 months.

For the primary outcome of pain, the results showed no significant estimated difference between groups (0.49, 95% CI [-0.3, 1.2], p=0.198). For exploratory outcomes, after 6 months, the cryoneurolysis group showed a statistically but not clinically significant reduction in 24-hour pain scores compared to sham (1.1, 95% CI [0.3, 1.9], P=0.009). This statistical effect disappeared at the 12-month follow-up (0.7, 95% CI [-0.2, 1.5], P=0.111). Functional performance measures produced mixed results. There was no significant difference between groups in sit-to-stand or isometric knee maximal voluntary contraction at either time point. The walk 40 meters test did show the capacity for walking increased in the cryoneurolysis group compared to sham, as seen by significantly faster time measurements at 14 days (1.6s, 95% CI [0.2, 3.0], P=0.025), after structured exercise (1.8s, 95% CI [0.1, 3.5], P=0.04) and at 6 months (2s, 95% CI [0.4, 3.6], P=0.015) follow-up. The clinical significance of these small differences was not reported. Patient-reported outcomes showed no significant differences in QoL.

This study was limited by multiple factors. There were some concerns about the risk of performance and attrition biases, potentially from patients pursuing alternative treatments. There was a potential for multiple testing effects, which may have increased the risk of drawing false-positive results. There was a high loss to follow-up (>20%) for all secondary time points.

Undesirable Effects

No serious or long-term complications were observed during or following RFA procedures. Two RCTs reported there were nonserious adverse effects (e.g., bruising, numbness, redness, tenderness upon palpation, and swelling), which were deemed possibly or probably related to the device or procedure.^63,65

Health Care Utilization

Six RCTs assessed the impact of RFA compared to sham or other interventions on medication usage (e.g., analgesics, opioids). Only a single study employed a validated tool to quantify medication regimens. The remaining trials relied on patient diaries. The assessment of medication use was confounded, as most studies were unable to discriminate whether the pharmaceuticals were targeting KOA or other co-morbid conditions.

Two RCTs reported on the comparative effects of RFA and GNB on medication use.^77,90 Ma, et al. used data from 112 participant diaries to assess analgesic medication use >6 months post-knee arthroplasty.⁹⁰ The proportion of participants in the RFA group, who needed analgesic drugs at 1, 3, and 6 months was notably lower than in the GNB group (16.36% vs. 43.64%, 22.64% vs. 46.30%, 25.49% vs. 64.15%, respectively). Additionally, a small RCT (N=30) reported results showing reductions in oral opioid medication use were similar in RFA and GNB groups at 6 and 12 months (RFA: 57%, 71%; GNB: 44%, 67%, respectively).⁷⁷

In a study population that spanned 2 publications, only 8 participants in the RFA group and 7 in the HA IAI group were taking opioid medications at baseline.⁹¹ No significant changes were observed from baseline to the 6- and 12-month follow-ups in the RFA and HA joint injection groups.^91,92 Overall, only 12 subjects were taking opioids from knee-related pain. Given the small sample size, it was difficult to determine the significance of the reduction. Participants, however, decreased their total daily dose of non-opioid medications after 6 months in the cooled RFA group, whereas the opposite effect was noted in the HA injection group.^91,92 At 12 months, there were no statistically different changes from baseline in either group with non-opioid pain medications (p = 0.6539).⁹²

In a series of 2 publications of the same population randomly assigned to receive RFA or IACSI, there were no differences between groups with opioid analgesic medication use at any time point.^93,94 There were 43% of patients in the RFA group who were taking opioids for reasons other than knee pain. The mean change in non-opioid medication use was greater in the RFA versus the IACSI cohorts at 6 months (RFA [n = 29], −34.5 ± 128.9 mg; IACSI [n = 32], 135.5 ± 391 mg; P = 0.02). Data for 12 months were not reported.

Potential Effect Modifiers

Effect modifiers considered were patient characteristics and procedural techniques that meaningfully impacted the results for the critical outcomes of pain, function, treatment success, and undesirable effects. Three RCTs and a single NRSI were identified, which assessed the effects of different procedural techniques. A single RCT investigated the effects of pre-procedural diagnostic nerve blocks.

A pilot RCT comprising 2 publications compared the effects of cooled genicular RFA to conventional RFA on 49 individuals with either chronic KOA or persistent knee pain >12 months following total knee arthroplasty.^95,96 The primary outcome was treatment success (i.e., the proportion of patients with ≥50% pain reduction at 3 and 12 months). At the 3-month assessment, treatment success was achieved in 4 of 23 patients treated with conventional RFA (17%) vs. 8 of 24 with cooled (33%) (P = 0.21).⁹⁵ At the 12-month follow-up, the proportion of patients with ≥50% pain reduction at 12 months was 22.2% (4/18) in patients treated with conventional RFA versus 22.7% (5/22) in patients treated with cooled RFA (P > 0.05).⁹⁶

In the KOA and post-surgical populations, the difference in the percentage of patients that reached ≥50% pain reduction between cooled and conventional RFA was not statistically significant. For secondary outcomes in the short and intermediate terms, the findings from the RCT showed no statistically significant differences in pain intensity and functional outcomes.⁹⁵ At long-term follow-up, there was a statistically significant difference in the mean absolute numerical rating scale favoring cooled RFA versus conventional RFA (P = 0.02). Differences between functional outcomes were not statistically significant.⁹⁶ No meaningful differences in the occurrence or severity of undesirable effects between cooled and conventional RFA were identified at any time point. In this RCT, no serious adverse events were reported. In addition to the RCT, a retrospective cohort study (N=340) found that cooled RFA provided greater statistical improvement in the VAS pain score compared to traditional RFA (P = 0.010) in the short term. However, the difference between groups (0.91 cm) was not clinically significant.⁹⁷

Sanatana-Pineda, et al. compared continuous and pulsed genicular RFA.⁹⁸ Patients (N=216) with KL grade 3–4 KOA suffering from pain (VAS score ≥5 for >6 months), and resistant to conservative treatments, were enrolled in the study. Outcomes were measured at 1-, 6-, and 12-month post-intervention. For pain, the between-group differences were statistically significant (P < 0.05) at all follow-up assessments in favor of continuous RFA. However, none of the absolute between-group differences were clinically significant (0.56 points at 1 month; 0.89 at 6 months, 0.52 at 12 months). The differences between groups in mean total WOMAC scores were statistically significant at all follow-up periods, favoring continuous RFA. The respective absolute mean-point differences between groups at 1, 6, and 12 months of 1.54, 1.48, and 2.84 did not achieve clinical significance. The percentage of participants with at least a 50% reduction of the pre-intervention (baseline) VAS scores significantly favored the continuous RFA group, with absolute differences at 1, 6, and 12 months of 14%, 31.7%, and 21.8%, respectively. There were no significant differences in the occurrence of undesirable effects throughout the study (P = 0.107).

Chou, et al. systematically reviewed and meta-analyzed the comparative efficacy of 3 RFA techniques (conventional, pulsed, and cooled).⁹⁹ A total of 20 eligible articles (including 605 patients) were included in the meta-analysis. After treatment, the patients had significant improvement in pain for all 3 RFA techniques compared with the baseline level for the 1-, 3-, and 6-month follow-ups (P < 0.00001). However, there were no significant differences in the efficacy among the 3 RFA techniques for all follow-up visits (P > 0.05). The 3 RFA techniques demonstrated significant improvement in pain for up to 6 months after treatment. Comparing the efficacy of the 3 RFA techniques for treating KOA, the results showed no significant difference in pain relief at the 1-, 3-, 6-, and 12-month follow-up visits.

A single RCT (N=54) investigated the effects of RFA with or without a pre-procedural diagnostic nerve block in the intermediate term.⁶⁴ A total of 58.6% of participants in the diagnostic block group and 64% in the no-block group had ≥50% pain relief at 6 months. The between-group difference was not significant (P = 0.34). There was also no statistically significant difference between groups in functional measures at 6 months (P = 0.39). Undesirable effects were not reported.

Mohamed, et al. aimed to investigate the efficacy and safety of using 3 needles as a new technique in genicular RFA and compared it to the classic single-needle approach in 50 participants diagnosed with chronic KOA that was refractory to conservative treatment.¹⁰⁰ The 3-needle technique demonstrated statistically superior results of pain (VAS) and functional (WOMAC) outcomes in the short and intermediate terms. The results were not clinically relevant at any time point for pain. The clinical relevance of functional measures was not reported. The 3-needle group reported >50% reduction in pain scores at rates of 60%, 84%, 76%, and 72% at the first week and first, third, and sixth months, respectively. Between-group differences, favoring the 3-needle technique, were 28% at 2 weeks, 1 month, and 3 months, and 36% at 6 months. Apart from transient pain at the site of needle insertion, patients in this clinical trial had not reported any complications, such as hemorrhage, infection, sensory, or locomotor affection during the follow-up period.

Cryoneurolysis vs. Other Active Interventions

Patients (N=480) who had unilateral KOA and received nonoperative intervention were enrolled in a U.S. multi-centered real-world registry.¹⁰¹ The study compared and contrasted 6 non-operative treatment modalities for KOA: cryoneurolysis with deep or both deep and superficial GNB (CryoDeep/Both), cryoneurolysis with superficial nerve block only (Cryo-Superficial), IA hyaluronic acid (IA-HA) injections, IA nonsteroidal anti-inflammatory drug injections (IA-NSAIDs), IA-CS injections, or IA-triamcinolone extended-release (IA-TA-ER) injections. Across the 6 groups, patients demographics included mean ages between 59-69 years, 65-85% female, >90% K-L grades 2/4, and were followed for 4 months. Pain and functional outcomes were assessed at baseline, weekly, and monthly, and were analyzed by overall trend, magnitude changes from pre-treatment to post-treatment, and distribution-based MCID scores. Multivariate linear regressions with adjustments for 7 confounding factors were used to compare follow-up outcomes among 6 treatment groups.

Pain severity was measured using the Brief Pain Inventory, short form (BPI-SF), and functional outcomes were assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOS). Medication use was also evaluated. The authors reported that the use of IA-TA-ER injections was associated with the lowest pain, the greatest pain reduction, and the highest prevalence of patients achieving MCID relative to other treatments (P < 0.001). Deep/Both-Cryo and IA-CS were associated with a higher prevalence of achieving MCID than IA-HA, IA-NSAIDs, and Cryo-Superficial (P 0.001). Use of IA-TA-ER was also associated with the greatest functional score, improvement from baseline, and the highest prevalence of patients achieving MCID than other treatments (P ≤ 0.003). Subgroup analysis by baseline opioid exposure showed that follow-up opioid use was the same between the cryoneurolysis and other cohorts in opioid-exposed patients (27% versus 27%). Follow-up opioid use was comparable between cryoneurolysis and other cohorts among those patients who were not taking opioids at baseline (19% versus 14%).

Limitations included those inherent to registry-based analyses (e.g., selection and reporting bias) and discrepancies among the different participating locations in the operational aspects of registry execution.

Post-TKA

Most of the RCTs studying ablative modalities for KOA excluded subjects with a prior TKA and therefore these studies have no applicability. In a systematic review^67,93 there is limited evidence and low certainty to support the use of genicular nerve RFA for chronic knee pain post TKA.

A RCT comparing neurolysis to LA in patients who were post-TKA with persistent pain included 28 subjects. The authors reported a reduction in pain over 3-6 months using both techniques without adverse effects. Sample size was not sufficient for confidence and the authors called for larger scale investigations.⁷⁷ Additional evidence consists of case reports¹⁰² and small retrospective series.¹⁰³

Clinical Guidelines and Positions of National and Specialty Organizations

Societal Guidance

American Academy of Orthopedic Surgeons (AAOS)¹⁰⁴

The AAOS guideline for the Management of Osteoarthritis of the Knee (Non-Arthroplasty) classified RFA as “denervation therapy,” along with chemical ablation.¹⁰⁴ The guideline states that “denervation therapy may reduce pain and improve function in patients with symptomatic OA of the knee.” The strength of this recommendation is noted to be limited due to inconsistent evidence and bias.

Recommendations are based on Evidence-Based Clinical Practice Guidelines (non-surgical) and include the following:

• Measures with strong recommendation, supported by 2 or more high-quality studies, include topical and oral NSAIDs, acetaminophen, supervised exercise, and patient education programs.

• Measures with moderate recommendations, derived from 2 or more moderate quality studies or a single high-quality study, include weight loss, canes or braces, neuromuscular training, and IA corticosteroid injection.

• Measures with limited recommendations based on low-quality evidence include dietary supplements, manual therapy, massage, acupuncture, pulsed electromagnetic field therapy, extracorporeal shockwave, PRP injections, and denervation.

Recommendations against HA injection, lateral wedge insoles, and oral narcotics.

The authors state there are 19 high-quality studies and 6 moderate level supporting IAI of corticosteroids, with the duration of benefit limited to 3 months.

Osteoarthritis Research Society International (OARSI) Guidelines⁵⁸

Recommendations use the GRADE methodology and include:

• Conservative measures, including both pharmacologic and nonpharmacologic, received a strong recommendation.

• IAIs with corticosteroids and hyaluronan received conditional recommendations for KOA and relief limited to about 12 weeks.

• Denervation, cryoneurolysis, and RFA were not listed for KOA.

American Society of Pain and Neuroscience Consensus Guidelines^105,106

Recommendations based on U.S. Preventive Services Task Force criteria:

• Genicular nerve RFA is recommended (Grade A, Level of evidence: I) for chronic OA knee and post TKA pain for mid-to-long term pain control and functional improvement. The panel does not rate a single modality of genicular nerve RFA as superior and states that they are an alternative to IAIs.

The guideline did not include GNB or cryoneurolysis as treatment options for KOA.

• Conservative measures including topical and oral NSAIDs, topical diclofenac and PT received Level 1, Grade A, Strong recommendation but should be avoided long-term or with co-morbidities. Opioids were not recommended.

• Corticosteroid injections were noted to provide short-term pain relief for KOA refractory to conservative measures Level 1, Grade B, Consensus Moderate. HA and PRP injections received Level 1, Grade 1, Strong recommendation as safe and effective.

• RFA of the SM [superomedial], SL [superolateral], and IM [inferomedial] genicular nerves is a safe and effective therapeutic option for treating knee pain secondary to OA, as well as pain refractory to TKA; Level 1, Grade A, Consensus Strong. The literature to support the pain refractory to TKA recommendation is reviewed in the post-TKA section above and is of very low to low quality.

• RFA of the SM, SL, and IM genicular nerves can significantly reduce knee pain and improve function in patients with KOA and pain refractory to TKA; Level 1, Grade A, Consensus Strong.

• Thermal or cooled RFA should be utilized when performing GNA; Level 1, Grade A, Consensus Strong.

• The LEARN best practice document states genicular nerve RFA may be used for treatment of knee OA Grade II-I B, and further research for long-term and repeat use is needed.¹⁰⁶

American College of Rheumatology/Arthritis Foundation Guideline¹⁰⁷

Recommendations were made using the GRADE methodology:

• Recommends using a comprehensive management plan with physical modalities and mind-body approaches. Exercise and topical and oral NSAIDs received a strong recommendation.

• IAIs with corticosteroids received a strong recommendation for KOA, while other injectants received a conditional recommendation. HA and PRP injections received a strong recommendation against their use for KOA.

• RFA is conditionally recommended for KOA.

• GNBs or cryoneurolysis were not mentioned.

Osteoarthritis Research Society International (OARSI) guidelines, informed by an evidence report, made a conditional consensus recommendation (Level 4A: ≥75% “against” & >50% conditional strength of recommendation) against using nerve block therapy for KOA.⁵⁸ The OARSI guidelines did not include RFA as a candidate treatment for KOA.

European Alliance of Associations for Rheumatology (EULAR) did not include GNB, RFA, or cryoneurolysis as a core non-pharmacologic intervention for the management of KOA.¹⁰⁸

International recommendations:

Indian Society for the Study of Pain Guidelines rates RFA for KOA as safe and effective Grade A, Level 1 evidence.¹⁰⁹

Canadian Agency for Drugs and Technologies say RFA may improve pain without increasing adverse events.¹¹⁰

National Institute for Health and Care Excellence (NICE) states RFA for KOA may be used by appropriately trained clinicians.

No organizational guidelines were identified that issued recommendations for the management of KOA using diagnostic GNB with or without RFA.

Analysis of Evidence/Rationale for Decision Making

The certainty of evidence for minimally invasive interventions (e.g., GNB) as a therapeutic modality for KOA is currently not supported by high-quality evidence. The evidence for GNB is very uncertain for improvement in pain or function. The overall benefits across outcomes were inconsistent and minimal. There is great uncertainty about their effects in the long-term, as the available evidence is limited. The very low certainty ratings across all comparisons indicate substantial uncertainty about the true effectiveness of GNB. The SMEs during the contractor advisor meeting (CAC) advised that GNB was useful diagnostically to predict response to RFA. Therefore, GNB for KOA is limited to use as a diagnostic modality to predict patient outcome for future management.

The use of related minimally invasive interventions (e.g., RFA) for KOA is currently not supported by high-quality evidence. There is moderate certainty evidence that genicular cryoneurolysis likely provides overall functional improvement and a clinically superior reduction of pain-related activity interference, but not pain intensity, compared to sham intervention in the short and intermediate terms. There is insufficient evidence to determine the superiority or inferiority of cryoneurolysis compared to RFA. There is low-quality evidence to support the use of cooled or pulsed RFA for knee OA. Further research could have an important impact, which may change the estimates of effect.

The societal guidelines are mixed with some strong support for the role of RFA or cryoneurolysis for management, and others align with the literature as uncertain impact. The SMEs in the CAC were overall supportive of RFA, as they explained that it expands treatment options with low risk of harm. This is particularly beneficial to those who have significant co-morbidities or contraindications to surgery, or who are seeking pain relief and improved mobility while engaging in other non-surgical interventions for long-term management. Therefore, despite some uncertainty, a limited coverage position is taken while further investigations clarify patient selection, long-term outcomes, and a better understanding of the effectiveness of the different modalities and techniques.

While there is some societal support for ablative procedures post-TKA, the level of evidence rating to support the recommendation was derived from the literature for OA and largely excludes the post-TKA population, so it is not generalizable to this group. Without supportive evidence, this is considered investigational.

F. Morton's Neuroma Nerve Injections

Coverage

1. Corticosteroid (with or without LA) injection may be used for the treatment of Morton’s neuroma.^111,112

Frequency: A single steroid injection for Morton’s neuroma may be administered per side.^111-114 Medical necessity for repeat injections will be subject to individual case medical review.

Summary of Evidence

Efficacy/Effectiveness

Anesthetic Block versus Anesthetic + Corticosteroid Injection

Two systematic reviews analyzed data from RCTs and NRSI on the effectiveness of adding corticosteroids to LA injections in patients with Morton’s neuromas.^111,112 A meta-analysis of 2 RCTs (mean follow-up time = 4.5 months; range 3 to 6 months) provided moderate certainty evidence of clinically relevant results favoring the combined intervention (WMD: -5.3, 95%CI: -7.5 to − 3.2). In the second review, the pooled mean pre-pain score was 6.62 in 84 patients. The mean post-pain score was 4.35 in 215 patients. The mean difference of 2.27 points was clinically significant, with a mean follow-up of 9 months. This review of non-comparative studies was judged to provide very low certainty evidence.

One additional study that was not included in any systematic review was identified. In an extension of an RCT, Hau, et al. evaluated the 5-year results of LA injections with or without corticosteroid injections for Morton’s neuroma.¹¹³ Since the original study found no statistically significant difference between the groups in outcome measures and failure rates at 1 year following the injection, the data was pooled for the purpose of this study. Thirty-four out of the original 36 patients (mean age = 62.6 years) responded to this study via postal or phone surveys. The initial corticosteroid injection remained effective in 22 out of 45 neuromas (49%) at 1 year. At the final follow-up, 16 out of the initial 45 neuromas (36%) continued to remain asymptomatic. For those participants who experienced effective pain relief at 1 year (22 of 45 neuromas), 73% (16 out of the initial 45 neuromas) reported continued effectiveness at 5 years. In addition to the cross-sectional design, the main limitation of this study was the sample size, which was powered for the purpose of the original RCT. This may have introduced type II errors (false negative results) in some of the outcome measures. Another limitation was that the secondary interventions occurred at different time points following the original injection, leading to varying follow-up intervals.

Undesirable Effects

A systematic review found that local adverse effects (e.g., numbness, swelling, pain, mild skin atrophy, depigmentation) at the injection site reportedly occurred in 0–27% of patients.¹¹⁵ No study described any serious adverse effects (e.g., hyperglycemia, infection, or tendon rupture).^114,115

Patient Experience

A systematic review stated that binary outcome measures from 6 studies demonstrated successful satisfaction following corticosteroid + LA intervention (34%, 95% CI: 21 to 49%) at a mean of 8.4 months.¹¹² Hau, et al. reported that 88% of the patients, after a single corticosteroid injection, were still satisfied with their outcome at 5-years post-intervention.¹¹³

Health Care Utilization

Two systematic reviews reported similar rates (30%, 33%) of eventual transition to surgery within 12 months after steroid injection.^111,114 Hau, et al. obtained survey results from 34 of 36 patients who 5 years earlier had received a single injection of LA with or without corticosteroid injection for Morton’s neuroma.¹¹³ Over the course of the study, almost 25% of neuromas received a second injection; however, only 5% of injections took place between 1- and 5-year follow-up. Overall, 44% (n = 20) of the initial cohort underwent surgical excision by the medium-term follow-up, including ≈13% between 1- and 5-year follow-up.

Potential Effect Modifiers

Choi, et al. systematically reviewed the literature and found no comparison studies that focused on the injection approach by anatomic site (dorsal, plantar, or web space).¹¹⁴

Analysis of Evidence/Rationale for Decision Making

There is moderate certainty evidence that the addition of corticosteroids to LA injections likely results in a clinically significant benefit on pain associated with Morton’s neuroma. There is low certainty evidence that anesthetic and corticosteroid injections may result in localized adverse effects. Therefore, the evidence demonstrates clinically meaningful benefit with acceptable risk, supporting a favorable net benefit and meeting the statutory standard for reasonable and necessary care under SSA §1862(a)(1)(A).

Most studies report a single corticosteroid injection for up to a 12-month follow-up.^111,114 Population-level data demonstrate significant heterogeneity across studies regarding the safety and effectiveness of multiple injections for Morton’s neuroma, making it unfeasible to establish generalized frequency parameters. Therefore, medical necessity for repeat injections will be subject to individual case medical review.

G. Occipital Nerve Blocks

Occipital neuralgia presents as chronic or recurrent pain originating in the posterior scalp and upper cervical region, often radiating unilaterally or bilaterally. This pain stems from irritation or entrapment of the occipital nerve (ON).

An occipital nerve block targets the greater occipital nerve but may also target the lesser occipital or third occipital nerve, depending on the location of pain. Some papers refer to greater occipital nerve block (GONB) even when encompassing the lesser occipital nerves.

Coverage

Occipital Nerve Injection (ONI) is considered reasonable and necessary for occipital neuralgia when all the following criteria have been met:

1. A positive diagnostic block, as defined by greater than 50% pain reduction after the procedure for the duration of the local anesthetic, to establish the diagnosis of occipital neuralgia.

2. A therapeutic ONI for the acute management of refractory occipital neuralgia, defined as:

   1. Documentation in medical records concludes that other etiologies of headaches have been excluded AND
   2. Headache is severe and debilitating AND
   3. Documentation of failure or contraindication to medical management.

Limitations

1. ONI can be performed unilaterally or bilaterally
2. ONI must be performed by an appropriately trained provider
3. ONI injectant may be a LA with or without corticosteroids. Any other injection will be non-covered.
4. Scheduled use (e.g., series) of ONI for headache management is considered investigational.
5. The use of ONI for any other headache type is considered investigational.
6. The use of RFA of the occipital nerves is considered investigational.

Frequency Limitation: A maximum of 4 ONI is allowed within 12 months.¹¹⁶

Summary of Evidence

Systematic Reviews

Mustafa, et al. conducted a SR/MA compromised of 8 studies (n=268) on the effectiveness of GONB in chronic migraine (CM).¹¹⁷ Using the Cochrane ROB tool, the reviewers reported low risk across all domains. However, there are ROB noted, including lack of blinding, uncertainty about randomization, selective reporting and some unknown risk in 2 of the 8 studies without concerns. The duration of the studies ranged from 4 weeks to 3 months. Meta-analysis of 5 of 8 studies reported low heterogenicity and showed favorable results but did not reach statistical significance. The studies are downgraded based on imprecision (small sample size and short-term follow-up), and ROB for low certainty evidence.

Evans, et al. conducted a SR/MA comprised of 12 RCTs (N=586) utilizing injection treatments for headaches with pain or tenderness in the occipital scalp.¹¹⁸ The meta‑analyses for the assessment of pain severity of nerve blocks compared with other treatment groups (i.e., neurolysis, PRF, and BTX-A) demonstrated a lack of improvement after 2 weeks. Statistically significant reductions were reported in headache frequency at 1- 6 weeks compared with baseline to inactive control injections. Limitations included self-reporting bias, a limited number of studies included, varied diagnoses (although all related to headache), injection techniques, medications, and modalities such as the use of nerve stimulator-guided injections.¹¹⁷

Velasquez-Rimachi, et al. performed a meta-analysis which included 3 RCTs (n=310) to evaluate GONB LAs alone or with corticosteroids to prevent CM.¹¹⁹ At 2 months follow up, GONB achieved a reduction in headache intensity, but not frequency. Trial sequential analysis of the RCTs was inconclusive. Limitations include very low certainty of evidence due to very serious ROB and imprecision due to small sample size, short duration of follow up, and variability in reported outcomes.

Ornello, et al. conducted a meta-analysis of 5 studies to evaluate the evidence of efficacy and safety of GONB in cluster headaches (CH).¹²⁰ The studies reported a decrease in headache severity, intensity, and duration. Limitations included the use of observational data, a lack of high-quality studies included in the analysis resulting in high heterogeneity, imprecision, wide variation among study designs, a short duration of follow up, and unclear ROB.

Shauly, et al. conducted a systematic review to assess the efficacy of GONB in the treatment of CM headaches treated with LA, corticosteroid or saline.¹²¹ GONB resulted in a significant decrease in headache severity as compared to saline controls (P < 0.0121). There were no serious adverse events. Limitations included variations of control and intervention groups (control groups in 3 studies were given LA, while the intervention included corticosteroids), the use of Jadad scale for ROB bias assessment, a small number of included studies, limited sample size, and short duration of follow-up.

Zhang, et al. conducted a SR/MA to investigate the efficacy of GONB with LA for migraine patients.¹²² Reviewers conclude GONB significantly reduces pain intensity and analgesic medication consumption for migraine patients with no increase in adverse events. There was no impact on headache duration. Limitations of this study included significant heterogeneity in pain intensity compared to control, limited study inclusion, relatively small sample size, utilization of simple evidence quality assessment, self-reporting bias, short duration of follow-up, and variations among interventions.

Gordon, et al. conducted a SR to evaluate the safety and effectiveness of GONB for short-term prevention of cluster headaches.¹²³ Reviewers concluded that there was a significant improvement in frequency, severity, and/or duration because of the GONB. There were 5 potentially irreversible adverse effects. Limitations include inconsistency across studies, the inclusion of lower-quality studies, a high ROB in a large proportion of included studies, and a short duration of follow-up.

Oliveria, et al. conducted a SR that included 2 RCTs and 20 non-randomized papers reporting on pulsed RFA of the GON for headaches.¹²⁴ The investigators concluded that, based on low-quality evidence, there was a benefit from PRFA of GON for occipital neuralgia, but the role for other headache types was unclear, and further high-quality research is needed.

Orhurhu, et al. evaluated the use of RFA for headaches in a SR that included 6 RCTs and 12 non-randomized studies.¹¹⁶ The report is challenged by significant variability in headache types, definitions, the type of RFA used, and the methodology of administration. There was overall pain relief at 3 months, and a longer duration (>90 days) was reported in some of the papers included. There were no serious adverse events.

Evans, et al. conducted a SR/MA that included 12 RCTs (N=586) of patients with occipital headaches treated with ONB.¹¹⁸ The reviewers reported improvement in pain severity with significant reduction “2.88 points at 5 to 20 min, 3.74 points at 1 to 6 weeks, and 1.07 points at 12 to 24 weeks.” Headache frequency was improved compared to baseline at 1 to 6 weeks. Using the Cochrane ROB tool, 5 RCTs were rated low risk, 3 moderate risk, and 4 high risk. Additional limitations include a lack of generalizability to the Medicare population as age <65, high variability among included trials, and short duration of follow-up.

Li, et al. conducted a meta-analysis on the use of GONB, which included 4 RCTs, and found a two-fold reduction in pain intensity for acute migraine at 30 to 60 minutes.¹⁸¹ Methodological concerns of this analysis include that while low heterogeneity was reported between the studies, the criteria for study exclusion were unclear. Also, the study methodology was assessed using the modified Jadad scale, and while the author’s report supports its use as high quality, the ROB for the individual studies was not reported.

Randomized Controlled Trials (RCTs)

Efficacy Outcomes

Malekian, et al. presented a single-site double-blind placebo-controlled RCT to examine the efficacy of GONB in 55 subjects (mean age 40.42 ± 12.23) suffering from episodic migraines without aura with steroid, lidocaine steroid + lidocaine, or saline.¹²⁵ No significant difference among groups was reported. No injection was superior to the placebo regarding the duration and severity of the headaches. Limitations of this study included: a small sample size resulting in the study being underpowered, 16 subjects were on preventive migraine medications when enrolled, limited follow-up, and the amount of the medication was not recorded in certain instances.

Chowdhury, et al. reported a double-blinded, RCT comparing episodic cluster headache patients receiving GONB (n=19) or placebo (n=20) with lidocaine and steroid.¹²⁶ The treatment group experienced −11.1 (95% CI: −8.5 to −4.4 reduction in headache frequency compared to the placebo −7.7 (95% CI: −11.8 to −9.8) with a mean difference of −3.4 (95% CI: −5.2 to −1.7, p<0.001). Although local bleeding and pain at the injection sites were observed, no serious adverse events occurred. Limitations include small sample size, lack of generalizability to the Medicare population, and short-term follow-up (4 weeks).

Ertilav, et al. randomized 35 subjects with CM to GON and 32 to GON PRF and followed them for 6 months.¹²⁷ They reported that both groups showed improvements at 1 and 6 months, and the GON PRF scores were lower at 6 months. Limitations include a lack of generalizability to the Medicare population (age 18-60 yrs), a lack of a control group, a small sample size, and no blinding.

Gul, et al. conducted a single-blinded RCT, which compared GONB to placebo in 44 patients with CM over a 3-month time period.¹²⁸ Both groups reported a lower number of headache days at 1 month. The effect persisted into the second and third months for the treatment group but not the placebo. No severe adverse events were reported. Limitations included a small sample size, ROB due to the randomization method, and short-term follow-up.

Inan, et al. conducted a double-blinded RCT in which 84 patients received either a GONB with saline or bupivacaine for CM.¹²⁹ Overall, they reported improvement in both groups, but a greater and more sustainable effect was seen in the bupivacaine group. The placebo group crossed over to the steroid at week 6 and reported greater improvements after crossover. Limitations include a small sample size and a very short duration of follow-up, especially for the placebo group.

Cohen, et al. conducted a double-blinded, RCT comparing PRF (n=42) to steroid injection (n=42) of the ON for occipital neuralgia.¹³⁰ Greater pain reduction was reported in the PRF group compared to ON injection at 6 weeks, which persisted for up to 6 months for pain relief. Limitations include short-term follow-up and unblinding at 6 weeks with crossover in those without benefit from initial treatment, so one cannot assess long-term outcomes.

Potential Effect Modifiers

Kissoon, et al. conducted a single center, prospective RCT to compare outcomes between an ultrasound-guided bilateral greater occipital nerve block (USGONB) at the C2 vertebral level versus landmark-based greater occipital nerve block (LGONB) at the superior nuchal line in 32 subjects with occipital neuralgia or cervicogenic headache.¹³¹ The results suggest that patients with occipital neuralgia or cervicogenic headache may benefit from greater pain reduction at 4 weeks from USGONB as compared to LGONB.

Babaoglu, et al. conducted a RCT in which 60 subjects with CM were allocated to distal versus proximal greater occipital nerve PRF treatment.¹³² They reported a reduction in headache frequency and severity for both groups, but greater in the proximal group.

Clinical Guidelines and Positions of National and Specialty Organizations

The American Academy of Pain Medicine (AAPM) Foundation published a SR/MA in 2022 with clinical practice recommendations using the GRADE methodology.¹³³ The committee concluded:

• GONB received a weak recommendation for use based on insufficient evidence for their use for CM prevention.
• For GONB, steroid(s) received a weak recommendation against their use vs the use of LA alone.

The European Academy of Neurology (EAN) 2023 guidelines for cluster headaches recommend ONB for cluster headaches.¹³⁴ This recommendation was based on consensus, and they acknowledge that the evidence is insufficient to issue evidence-based guidelines. The guidelines also incorporate oral and intravenous (IV) steroid use for headache management.

Congress of Neurological Surgeons (CNS) updated their previously conducted SR, adding 6 additional papers to the report on the role of ONB for the management of medically refractory ON.¹³⁵ The additional literature did not change their guidelines, which state “Clinicians may use occipital nerve stimulation as a treatment option for patients with medically refractory occipital neuralgia (Level III)”.

The American Headache Society (AHS) recommends GONB as a Level A (Must Offer) recommendation for patients needing parental migraine therapy in the emergency department.¹³⁶ The society conducted a SR that included 26 RCTs for injectable treatment, which includes ONB.

International Headache Society¹³⁷ published global practice recommendation for acute pharmacological treatment of migraine in which they state: “Evidence for the use of nerve blocks, IV magnesium or sodium valproate is scarce. These treatments can be evaluated if all other options are unavailable, contraindicated, or ineffective.”

Analysis of Evidence/Rationale for Decision Making

Patients receiving nerve blocks with or without glucocorticoids for occipital neuralgia, cervicogenic headache, CM, and cluster headaches may experience temporary but immediate pain relief based on very low or low certainty for effectiveness. There is questionable benefit of the addition of corticosteroids over LA alone. There is a lack of evidence for effectiveness for long-term use for headache management.

The American Headache Society has recommended GONB as a therapy for acute migraine refractory to parental medication in the emergency room based on low-quality (Level III evidence). Typically, strong recommendations are supported by higher-quality evidence, creating a conundrum. However, this LCD does not address acute pain, and therefore, this indication is beyond the scope of this LCD, leaving it at the individual MAC's discretion.

The evidence for the role of GONB and RFA for other headache types, including cervicogenic and cluster headaches, is also very low and of low quality. The appropriate patient selection, standardization of the procedure, including what injectant to be used, and provider qualifications to perform the procedure are not clearly established. The lack of generalizability to the Medicare population in these studies, when the majority included patients under age 60, is a concern, especially as the risk in an older population with greater co-morbidities is not established, raising safety concerns. Further investigation is necessary to address these gaps; therefore, this is considered investigational.

Despite the low-quality evidence, there are no nonsurgical treatment options for ON refractory to medical management. The block has become the acceptable standard for diagnosis and evaluation for surgical management. Therefore, the GONB will be covered for these indications, as well as a salvage therapy for acute pain refractory to medical management. However, in the absence of long-term studies, the use of these blocks as a chronic/repetitive treatment strategy, GON/RFA for indications other than ON requires further investigation.

H. Posterior tibial nerve block(s)

Background

Tarsal tunnel syndrome (TTS), otherwise known as posterior tibial neuralgia, is a compressive neuropathy affecting the posterior tibial nerve within the tarsal tunnel. This causes pain to the heel and the plantar aspect of the foot, numbness, paresthesia, and in severe cases, muscle weakness and atrophy. Care is usually conservative measures, with surgical decompression reserved for refractory cases.¹³⁸

Coverage

Posterior tibial nerve block(s) at the tarsal tunnel for the treatment of chronic foot pain are considered investigational and non-covered.

Summary of Evidence

While scoping reviews sit outside the traditional effectiveness-focused evidence hierarchy, they inform an understanding of the evidence landscape. A scoping review of 32 studies on the management of TTS was conducted.¹³⁸ Of the 32 studies, all were case series except for 3 cohort studies, which included 29, 44, and 107 patients. Outcome measures and treatment were highly variable, resulting in significant heterogeneity between studies. All used surgical decompression of the posterior tibial nerve as management. Seventeen studies did not report a trial of conservative management, and there was not sufficient evidence to determine the effectiveness of corticosteroid injections. Scoping reviews must be supplemented by systematic reviews or well‑designed primary studies that allow for evidence-informed coverage determinations.

A retrospective study evaluated 45 subjects with chronic foot pain who underwent a tibial nerve block in a single center.¹³⁹ The authors reported that at 7 weeks of follow-up, 38 subjects (53%) experienced pain relief, and 22% improved walking distance. Benefits were present to 18 months in 45% of the initially successfully treated feet. Limitations included the non-comparative study design, small sample size, and lack of a standardized assessment tool indicative of very-low certainty of the effectiveness of the blocks.

Atesok, et al. studied a retrospective cohort with 218 patients diagnosed with TTS who received US-guided posterior tibial nerve injections. After the injections, 169 patients (77.5%) did not go on to tarsal tunnel release (TTR) (nonsurgical group) and 49 patients (22.5%) underwent TTR (surgical group).¹⁴⁰

Analysis of Evidence/Rationale for Decision Making

The literature on the role of posterior tibial nerve block(s) at the tarsal tunnel is very low certainty and there are no experimental studies that assess the role of nerve blocks or denervation for management of this condition. Therefore, this is considered investigational.

I. Pudendal Nerve Injections (PuNI)

Pudendal neuralgia (PN) is a neuropathy of the pudendal nerve resulting in chronic pelvic pain and is not well understood.¹⁴¹ Diagnosis is made by the Nantes criteria consisting of pain in the anatomical territory of the pudendal nerve that worsens with sitting, does not disrupt sleep and without objective sensory loss or other etiology to explain pain. Diagnosis is confirmed by pudendal nerve block.¹⁴²

Coverage

A diagnostic pudendal nerve block (PuNB) may be used to confirm or exclude PN in patients in which PN is highly suspicious based on the Nantes criteria.¹⁴²

The use of therapeutic PuNB, PuNI or RFA of the pudendal nerve are considered not medically reasonable and necessary and are non-covered.

Frequency Limitation: A single diagnostic block may be performed. In rare circumstances in which there is concern that the pain generator was missed, a second diagnostic block may be performed.

Summary of Evidence

Systematic Review/Meta-analysis

A SR/MA by Andiman, et al. reviewed 37 studies that explored any intervention for PN, including surgical, injections, nerve stimulator placement, and pulsed RFA.¹⁴¹ The investigators rated 95% of the evidence quality as Grade C, with significant heterogeneity between the studies. No treatment was found to be superior for pain relief.

Randomized Controlled Trials

Labat, et al. carried out a multicenter RCT (N=201) to assess the effectiveness of combining corticosteroids with LAs versus anesthetic-only PuNB in patients with pudendal nerve entrapment (PNE).¹⁴³ No significant difference between the groups was detected for the various pain assessment procedures, functional criteria, or quality-of-life measures. The authors concluded that corticosteroids provide no additional therapeutic benefits compared with LA PuNB and should, therefore, no longer be used.

Elsawy, et al. conducted a RCT in which patients with PN were randomized to PRFA (n=38) or pulse-dosed RFA (n=39) and followed for 6 months.¹⁴⁴ The authors reported a non-significant reduction in VAS scores with similar results for both methods. This is limited by a lack of control group, short-term follow-up, small sample size, and lack of blinding.

Fang, et al. conducted a RCT that included 80 subjects with PN who received NB or RFA and were followed for 3 months.¹⁴⁵ The authors reported improvement in both groups after the procedure and found the improvement to be sustainable in the RFA group (92.1%) compared to NB (35.9%) at 3 months. Limitations include small sample size, lack of control, and concerns for generalizability to the US population and age < 65.

Observational studies

A prospective study reported on 26 subjects who received CT-guided percutaneous pulse-dose RFA for PN.¹⁴⁶ The investigators reported improvement in VAS scores from baseline (mean 3.8 ± 1.7, p=0.05) to 1.5 ± 1.1 at 6 months in the following months, with continued benefit up to 1 year. Minor adverse events were reported. The sample size was too small to determine if these findings are statistically significant.

A retrospective case series provided preliminary single-arm data. Levin, et al. reported on a study involving 101 patients with PN (mean age 43.6 years) who received fluoroscopy-guided trans-gluteal PuNB.¹⁴⁷ Therapeutic success was defined as achieving at least 30% relief of pain. Using worst-case analysis, the success rate for 2 weeks was 49.4% (95% CI: 38.5%, 60.3%) and 23.5% (95% CI: 14.3%, 32.7%) lasting at least 1 month. A total of 14 out of 81 patients (17.3%) reported some type of adverse effect from the block, with the most common symptom reported being temporary pain flare-up and temporary leg weakness/numbness.

A retrospective cohort study followed 67 patients with PN who underwent pudendal nerve injection with LA and corticosteroid, and completed a VAS score at 1, 3, 6, 12, and 24 weeks post-intervention.¹⁴⁸ Effectiveness, defined as 50% improvement in pain scores, was achieved in 60-75% at 1 month and declined to 33-58% at 24 months, depending on anatomical location. This is limited by retrospective design and the inherent associated methodological concerns.

Another retrospective report of 70 patients who underwent high voltage, long duration PRF under CT-guidance for PN reported improvement in pain up to 12 weeks after the procedure, with improved quality of life and depression scores.¹⁴⁹ The VAS scores were decreased compared to baseline at all time points (1, 4, and 12 weeks), but progressively increased over time. The patients were required to have a diagnostic pudendal block before the procedure, but the cut-off for a successful block was not reported. Limitations include small sample size, lack of control, unclear inclusion criteria, and risk of placebo effect.

There is insufficient literature to address safety in the PN population. PuNBs have been used historically in obstetrics and are not recommended for routine use due to risk of hematoma, infection, nerve injury, systemic toxicity, and inconsistent results, with 10-50% of blocks ineffective for satisfactory analgesia.¹⁵⁰

Clinical Guidelines and Positions of National and Specialty Organizations

European Association of Urology guideline on chronic pelvic pain has concluded, “There is weak evidence base for these [GIB, PuNB] interventions for chronic non-malignant pain.”¹⁵¹ An injection of LA and steroid at the site of nerve injury may be diagnostic. Differential block of the pudendal nerve helps to provide information in relation to the site where the nerve may be trapped.¹⁵¹

Analysis of Evidence/Rationale for Decision Making

The evidence for therapeutic PuNB or RFA for the treatment of PN is inconsistent. While there are some low-quality reports that demonstrate weak positive results, the majority of the literature, including 2 of the 3 RCTs and the single SR/MA, do not demonstrate positive results.^141,143-145 Additionally, there is concern about safety risk in the obstetrical literature, which may not apply to the PN population; however, there is insufficient safety data on the use for PN to exclude this risk.

J. Suprascapular Nerve Injections (SSNI)

Background

Chronic shoulder pain can result from several causes, including adhesive capsulitis or frozen shoulder, rotator cuff tear, shoulder impingement (SIS), OA, RA, or hemiplegic shoulder pain as chronic pain conditions. The suprascapular nerve is the predominant sensory nerve to the shoulder, so blocks and RFA of this nerve are explored as a potential treatment option for chronic shoulder pain.¹⁵² Management may include PT, medications, and, if unsuccessful, IAI.

Coverage

A single suprascapular nerve injection (SSNI) may be used as a diagnostic modality for chronic shoulder pain conditions when needed for diagnosis or surgical planning.

Therapeutic SSNI is covered when all the following are met:

1. The patient has a clinical diagnosis of shoulder adhesive capsulitis¹⁵³ or degenerative or inflammatory shoulder arthritis (i.e., acromioclavicular [AC] joint or glenohumeral joint )¹⁵⁴ AND

2. If imaging is performed, it is consistent with this diagnosis and not another etiology AND

3. The patient’s pain is severe, or loss of active and passive ROM of the glenohumeral joint is limiting activities of daily living (ADLs), AND

4. Documented trial of conservative measures without significant objective clinical improvement for at least 12 weeks, measured on a pain or disability scale¹ AND

5. There was ≥ 50% improvement in pain or function from the diagnostic injections (with the duration of relief being consistent with the agent used).

6. Repeat SSNI are permitted if there is ≥ 50% sustained improvement for at least 2 months after the last SSNI.

One repeat injection is permitted if there is ≥ 50% improvement from the initial injection.¹⁵⁴

Limitations

1. SSNI may be a LA with or without corticosteroids; any other injection will be non-covered.

2. The use of SSNI for any other indication is considered investigational.

3. The use of RFA of the suprascapular nerve is considered investigational.

4. More than 2 therapeutic SSNI in 12 months is considered rare and may trigger targeted medical review.

Summary of Evidence

Efficacy/Effectiveness Outcomes

Systematic Reviews

Scattergood, et al. assessed the effectiveness of suprascapular nerve blocks SSNB compared to the standard of non-operative care in shoulder pain reduction at 3 months in 5 RCTs (N= 343; range 40-180).¹⁵⁵ Authors stated SSNB is an effective method of treatment for chronic shoulder pain, with a suggestion that it may be superior to routine non-operative care: placebo, physiotherapy or targeted steroid injections. The systematic review had several limitations. The reviewers assessed ROB and had some concerns in 2 studies regarding deviation from the intended intervention and measurement of outcome. Other limitations include short follow-up periods, injectant variability, and variability in reporting.

Chang, et al. performed a meta-analysis comprised of 11 RCTs to evaluate the effectiveness of SSNB at different timings after administration compared with PT, placebo, and IAIs in patients with chronic shoulder pain.¹⁵⁶ The authors reported improvement in pain as compared to placebo and PT, but not to IAIs. This report was limited by moderate to high heterogeneity, short duration of follow-up, moderate sample size and some concerns about ROB.

Bennett, et al. conducted a SR/MA of the role of SSNB for management of frozen shoulder to improve movement at the glenohumeral joint.¹⁵⁷ This evidence synthesis included 12 RCTs (n=702) of which 8 were considered by the reviewers to be at a low ROB and 4 with some concerns. Comparators included in the meta-analyses were IA steroid injections and physiotherapy. The primary outcome was any functional patient-reported outcome measure (e.g., SPADI, Constant-Muley Score). Secondary outcomes were the VAS for pain and ROM.

The reviewers reported that the results suggest treatment with SSNB is favorable when compared to IAI. Statistically significant improvements favoring the use of SSNB over IAI were seen in SPADI (4.75- point difference) and external rotation (11.6° difference) at the last follow-up. The SPADI improvement remained significant when only RCTs directly comparing SSNB and IAI were analyzed. There was no significant difference between studies comparing SSNB + IAI and IAI alone. The reviewers also found a statistically significant difference in pain (VAS) outcomes favoring SSNB versus physiotherapy.

Further analysis of this review revealed more discrete findings:

• There is moderate certainty evidence (3 RCTs; downgraded for inconsistency) that SSNB demonstrates a trivial (not clinically significant) benefit compared to IAI [-3.73 (95% CI: -7.05 to -0.40)] for functional outcomes as reported using the SPADI tool.
• There is very-low certainty evidence (3 RCTs; downgraded for imprecision and very serious inconsistency) that SSNB + IAI results in no difference compared to IAI [-9.79 (95% CI: -23.05 to 3.46)] for functional outcomes as reported using the SPADI tool.
• There is moderate certainty evidence (7 RCTs; downgraded for inconsistency) that SSNB with or without IAI produces a trivial (not clinically significant) benefit compared to IAI [-4.75 (95% CI: -8.11 to -1.39)] for functional outcomes as reported using the SPADI tool.
• There is low certainty evidence (6 RCTs; downgraded for imprecision and inconsistency) that SSNB with or without IAI demonstrates a favorable but not statistically significant difference compared to IAI [11.64° (95% CI: -0.05 to 23.33)] on external rotation of the shoulder.
• There is low certainty evidence (3 RCTs; downgraded for imprecision and inconsistency) that SSNB with or without IAI demonstrates no difference compared to IAI [-0.61 (95% CI: -2.21 to 0.99)] on pain intensity.
• There is high certainty evidence (3 RCTs) that SSNB with or without IAI demonstrates a trivial benefit compared to physiotherapy [-0.31 (95% CI: -0.53 to 0.10)] on pain intensity.
• There is low certainty evidence (2 RCTs; downgraded for imprecision and inconsistency) that SSNB with or without IAI demonstrates no difference compared to physiotherapy [-7.84 (95% CI: -17.65 to 1.96)] on functional outcomes as reported using the SPADI tool.
• There is low certainty evidence (2 RCTs; downgraded for imprecision and inconsistency) that SSNB with or without IAI demonstrates no statistical difference compared to physiotherapy [10.37° (95% CI: -0.40 to 21.15)] on external rotation of the shoulder.
• There is moderate certainty evidence (2 RCTs; downgraded for imprecision) that SSNB with or without IAI demonstrates no difference compared to physiotherapy [3.29 (95% CI: -1.20 to 7.86)] on functional outcomes as reported using the Constant-Murley Score.

A SR/MA of SSNB included 18 studies (n=704), including 11 RCTs and 7 observational studies.¹⁵² Indications included adhesive capsulitis, RA, chronic pain, rotator cuff tear, any pain type, noninflammatory pain, impingement, OA, and AC joint pain. Meta-analysis could not determine if SSNB was more effective for any particular indication. The reviewers concluded that SSNB improves pain for all causes. This report is limited by a lack of standardized inclusion criteria, extreme variability in indications, technique, outcome assessment, and follow-up duration. Due to the high heterogeneity and methodological concerns, conclusions are not supported by the evidence presented.

Hou, et al. conducted a SR/MA on the role of SSNB for the management of pain from hemiplegic stroke.¹⁵⁸ There were 8 included studies with sample sizes from 10 to 64 and a wide variation in control methodologies. While the study favors a positive effect of SSNB for hemiplegic stroke, heterogeneity, small sample sizes, and short-term follow-up resulted in low-confidence evidence.

Harley, et al. performed a meta-analysis of RCTs for the use of SSNB as compared to IAI for adhesive capsulitis. It included 8 RCTs (N=452) subjects.¹⁵³ Functional outcome assessments included SPADI and Constant-Murley Score. They reported heterogeneity among the included studies, and ROB assessment was reported as low (4), some concerns (3), and high risk (1). The reviewers concluded there was greater pain relief, improved function, and mobility for up to 12 weeks in the SSNB group as compared with IA steroid injections. Limitations include heterogeneity and small sample sizes of the included studies, which limit the confidence in the evidence.

Shanahan, et al. conducted a double-blinded RCT with 83 people with chronic shoulder pain from inflammatory arthritis and/or degenerative disease receiving a SSNB or placebo and followed for 12 weeks.¹⁵⁴ The reviewers reported improvement in pain scores, disability scores, and improved ROM scores compared to placebo, with sustained improvement to week 12. There were no serious adverse events.

Scattergood, et al. conducted a SR to evaluate SSNB to standard non-operative care for chronic shoulder pain at 3 months.¹⁵⁵ Five RCTs were included, representing variable etiologies, interventions, and study populations. Two studies compared corticosteroids + LA with positive improvement, while LA alone did not show the same level of effectiveness. This report is limited by its high heterogeneity and short-term follow-up.

Suprascapular Ultrasound versus Landmark-Guided

A SR included 53 studies evaluating different injection methods for SSNB. The reviewers found indirect surface landmarks to be the most common approach reported in 21 studies and ultrasound guidance in 16 studies, while fluoroscopy and CT were only used in 1 study each. The types of injectant (LA and corticosteroids), dosing, and use of post-procedure physiotherapy were also variable. There is a lack of consensus for standardized practice of SSNB injection procedures.¹⁵⁹

A RCT compared 72 subjects with shoulder pain for >3 months to receive US-guided suprascapular nerve block (US-SSNB) or landmark-guided suprascapular nerve block (LG-SSNB).¹⁶⁰ At 3 months post injection, significant decreases in VAS, Shoulder Pain and Disability Index SPADI and Health Assessment Questionnaire (HAQ) scores were observed in both SSNB groups. This study has some concerns due to the short-term assessment.

A RCT with 50 subjects experiencing shoulder pain received SSNB under ultrasonographic guidance with an anatomical landmark‑guided (LMG) technique.¹⁶¹ Both the groups showed statistically similar improvement of VAS, ROM and SPADI at 4‑weeks. This study has some concerns due to the short duration of follow-up, limited sample size, lack of blinding and some concerns for ROB.

A small RCT compared ultrasound guided RFA of the suprascapular nerve to the injection block technique in 20 subjects at a single site [Egypt].¹⁶² At 6 months, no pain was reported using VAS score in 6 out of 10 subjects who were in the RFA group and 3 out of 10 for injections. This study had a high ROB due to the uncertainty of the randomization process, allocation concealment, and lack of blinding. An additional limitation was the very small sample size.

A RCT evaluated the effectiveness of SSNB with corticosteroid + LA or saline in 64 patients with hemiplegic shoulder pain after stroke.¹⁶³ In 29 subjects who received SSNB, there was a mean VAS reduction of >18 mm compared to placebo, lasting for 12 weeks. Limitations include a small sample size and short-term follow-up.

Undesirable Effects

Annison, et al. evaluated the physical harm associated with SSNB in the non-surgical management of shoulder pain.¹⁶⁴ This systematic review included 5,062 participants across 111 studies. A total of 168 individual episodes of harm were reported among 4,142 participants (4%) receiving SSNB intervention. Local pain and bruising were the most frequently reported harm reported with a low rate of 50 out of 4,142 (1.2%), but some serious adverse events were reported. Limitations of this systematic review include variability in terminology, follow-up, and techniques utilized, and a lack of reporting across included studies.

Potential Effect Modifiers

Effect modifiers considered were patient characteristics and procedural techniques that meaningfully impacted the results for the critical outcomes of pain, function, and undesirable effects. In a single prospective randomized trial (N=72), Saglam, et al. compared the effectiveness of US-guided injection to the landmark-guided SSNB group, where both groups achieved statistically significant improvements in pain scores at 3 months as compared to baseline.¹⁶⁰ VAS scores at baseline were 7.80 ± 2.17 as compared to 3.33 ± 2.12 at 3 months post nerve block in the landmark-guided blind nerve block group (P < 0.01) versus 3.33 ± 2.12 to 3.13 ± 1.96, respectively, in the US-guided group (P < 0.01). There were no injection-related side effects reported in either group.

Clinical Guidelines and Positions of National and Specialty Organizations

American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society
Reports on 2 retrospective reviews (N=89) that demonstrated patient benefit in shoulder pain following SSNBs, but lacked a comparison to LA with and without corticosteroid. No recommendation was made.¹⁶⁵

A Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)—part III, nerves of the upper limb (statement no. 3) states “Ultrasound-guided SSNB results in pain relief and improves ROM in patients with chronic shoulder pain, without clear superiority compared to a palpation-guided procedure.¹⁶⁶ Level of evidence: 3, Ultrasound-guided suprascapular nerve block with anesthetic and steroid is a safe and effective method for the management of chronic shoulder pain. Level of agreement: 97.8%” It also says (statement no. 4) “Ultrasound-guided PRFA of the suprascapular nerve for adhesive capsulitis combined with PT provides good clinical outcome at 12 weeks follow-up. Level of evidence: 2 Clinical trials demonstrate that the application of PRF stimulation on the suprascapular nerve under ultrasound guidance reduces pain intensity, improves shoulder range of movement, and can enhance quality of life at 12 weeks of follow-up. The combination of PT and radiofrequency is reported as more effective when compared with PT alone. Level of agreement: 88.9%” In statement no. 5 is states “Ultrasound-guided SSNB provides better pain relief and better functional results compared with subacromial injection in patients with symptomatic rotator cuff tears.” Level of evidence: 3, Full-thickness rotator cuff tears cause traction and tension on the suprascapular nerve, which is the dominant motor supply of the supraspinatus and infraspinatus muscles. A single randomized, double-blinded, controlled trial on 42 patients with rotator cuff tears demonstrated the superiority of ultrasound-guided SSNB compared with ultrasound-guided subacromial steroid injection. Level of agreement: 88.9%.”¹⁶⁶

Analysis of Evidence/Rationale for Decision Making

Low certainty evidence suggests that SSNB, compared to sham intervention, may result in a clinically significant reduction in chronic shoulder pain. It is uncertain about the effect of RFA compared to other percutaneous procedures on immediate pain relief, undesired events, and health care utilization (very low certainty of evidence). Societal guidelines are based on low-quality evidence (Level III). The role of SSNB for the management of chronic shoulder pain is inconclusive and requires further investigation and standardization of practice.

Two indications are exceptions. The evidence supports that SSNB for adhesive capsulitis is non-inferior to IAI¹⁵³ and evidence from a double-blinded, placebo-controlled trial demonstrates improvement for inflammatory arthritis for 12 weeks.¹⁵⁴ Therefore, limited coverage to aid in improving pain and mobility to allow full participation in physiotherapy and ADLs is included. Due to the lack of long-term data, repeating the injection beyond 12 weeks is not supported by evidence.

K. Trigeminal Neuralgia Nerve Blocks

Trigeminal neuralgia (TN) is a neuropathic pain condition affecting the trigeminal nerve, resulting in shock-like pain along the nerve pathway. Initial management includes medical management and intervention reserved for cases in which medical management fails.¹⁶⁷

Coverage

A diagnostic nerve block can be used for patients with clinical symptoms consistent with TN to confirm the diagnosis.

Radiofrequency neurolysis (RFN) is considered medically reasonable and necessary for the treatment of TN when ALL the following are met:

1. Condition has been present at least 6 months⁵⁵ AND
2. Patient is non-responsive to medical therapy (such as carbamazepine or oxcarbazepine, phenytoin, baclofen) or intolerant of medical therapy ^169,170AND
3. Patient is not a good surgical candidate or declines surgical intervention.^169,170 AND
4. Patient has had at ≥ 50% improvement after diagnostic trigeminal nerve block.

Frequency Limitation: Limited to (2) Radiofrequency Treatments (RFTs) within a rolling 12 months.^55,168

Non-covered: Therapeutic trigeminal nerve injections and denervation of the trigeminal nerve for any diagnosis other than TN.

Summary of Evidence

Systematic Reviews

Moore, et al. systematically reviewed the evidence with an aim to identify effective treatments that relieve acute exacerbations of TN pain within 24 hours of administration.¹⁶⁹ Of the 17 included studies, a single retrospective case series (N=13) included PNIs in conjunction with the oral administration of carbamazepine.¹⁷⁰ Patients reported complete relief of pain within 1-2 minutes following an anesthetic injection. The reviewers concluded that weak evidence exists to support the use of lidocaine nerve blocks. The main limitations reported by the reviewers were the low classification of study design, the small number of participants, and the high ROB.

Randomized Controlled Trials (RCTs)

No RCTs were identified that compared the discrete effects of PNIs to inert or active interventions on efficacy/effectiveness outcomes.

Non-Randomized Studies of an Intervention (NRSI)

A case series retrospectively analyzed data from 72 patients at 1 month, 48 patients at 3 months, and 27 patients at 6 months post-injection with a combination of lidocaine and triamcinolone.¹⁷¹ There was a statistically significant difference in pain intensity and frequency between baseline and post-procedure at 1, 3, and 6 months (P=0.000). In addition to the non-comparative design, this study was limited by the small number of participants, a high loss to follow-up, and uncertain applicability to the U.S. Medicare population.

A retrospective paper reported on 1,600 patients (2,138 procedures) with idiopathic TN with average follow-up time between 68.1 ± 66.4 months (range, 12–300 months).^168,172 They found that 76% (n=1216) were successfully managed with a single procedure. At 10-year follow-up, 52.3% of the patients who underwent a single procedure and 94.2% of the patients who underwent multiple procedures had experienced pain relief; at 20-year follow-up, 41 and 100% of these patients, respectively, had experienced pain relief.

Undesirable Effects

A SR reported adverse effects including local irritation (e.g., stinging, burning, numbness), bitter taste or numb throat, numbness, bitterness, hypoesthesia, dizziness, ptosis, insufficient block, mild somnolence, mild dizziness, tinnitus, ataxia, transient facial asymmetry, mild HTN, fatigue, and nausea. Four studies failed to report the occurrence of adverse events, and 4 studies reported no adverse events appeared.¹⁶⁹

Elsheikh, et al. indicated there were no serious adverse events reported during or after the interventional procedures. Seven patients had hematomas at the site of the puncture. Six patients in the control group and 4 patients in the calcitonin group had some degree of numbness and paresthesia on the side of the face that improved within 2 weeks.¹⁷² Similarly, a small case series described 2 complications. One patient had prolonged painless paresthesia related to the procedure area lasting about 1 week and 2 patients had ecchymosis at the procedure area.¹⁷¹

In a large retrospective report, complications included diminished corneal reflex (5.7%), masseter weakness and paralysis (4.1%), dysesthesia (1%), anesthesia dolorosa (0.8%), keratitis (0.6%) and transient paralysis or Cranial nerves III and VI (0.8%).^168,172

Clinical Guidelines and Positions of National and Specialty Organizations

The Royal College of Surgeons of England (2021)

The Royal College of Surgeons published a guideline for failed first-line treatment with medical management and failure of selective laser trabeculoplasty management, which outlines the use of “infiltration/block anesthesia to trigger point” as an acute adjuvant medication when provided by dentally trained clinicians with a weak recommendation. Lidocaine 2% 1:80000 adrenaline can be used in combination with bupivacaine or ropivacaine for longer relief. With weak recommendation, BTX-A may be administered by a specialist. With no consensus on dose or administration techniques and delayed onset, this should only be considered for medium-term TN management.¹⁷³

The European Academy of Neurology (2019)

The European Academy of Neurology performed a systematic review of the literature to provide recommendations for the guideline on TN injections. “Based on very low quality of evidence, a weak recommendation is given that BTX-A is used as add-on therapy for medium-term treatment of TN.”¹⁷⁴

Trigeminal Neuralgia Radiofrequency

Efficacy/Effectiveness

RFA versus Sham

A single RCT compared the effectiveness of trigeminal percutaneous RFA for patients with classical TN who had failed to respond to drug treatment.¹⁷⁵ Thirty participants were randomized to receive either RFA or a sham procedure. Pain reduction was stable through 1-month post-procedure with an absolute between-group difference of 5.4 points, which was clinically significant. This trial was judged to have a low ROB. Limitations included the small sample size (imprecision) and the lack of consideration given to different technical approaches that may have impacted effect measures (indirectness).

RFA versus other percutaneous strategies [balloon compression [BC], glycerol rhizotomy [GR], and microvascular decompression [MVD])

Three systematic reviews, 2 with meta-analysis, provided very low certainty evidence comparing RFA to 1 or more other percutaneous strategies for treating patients with TN.^52,167,176 RFA showed a superior outcome of immediate pain relief compared to GR in 2 reviews of patients with non-multiple sclerosis (MS)-related TN,^52,176 while another SR/MA focused on MS-related TN found no differences in terms of immediate pain relief or pain recurrence.¹⁶⁷ Two reviews meta-analyzed data comparing RFA with BC.^52,167 Both reviews reported that the comparison between RFA and BC showed similar rates of immediate pain relief and pain recurrence. Yan, et al. found no difference in immediate pain relief between RFA and MVD; however, RFA was associated with an increased risk of pain recurrence compared with MVD.⁵²

Two NRSI that were not included in a systematic review provided retrospective analyses of the observed effects of RFA for TN. Habib, et al. included only patients suffering from intractable classical TN.⁵³ Sozer, et al focused on patients with MS-related TN.⁵⁴ Both studies found there was no significant difference in immediate pain relief between RFA and MVD. Limitations included those inherent in observational study designs, a high risk of confounding, and indirectness.

Undesirable Effects

A systematic review reported that RFA was associated with an increased incidence of postoperative anesthesia compared with GR and MVD.⁵² Data pooled from 9 NRSI showed that compared with RFA, MVD had a lower risk of requiring a secondary procedure or facial numbness.¹⁷⁷ In contrast, MVD was more likely to increase the risk of hypoacusis (hearing loss) and hypesthesia than RFA. A small retrospective study reported there was no significant difference (P 0.81) in complication rate between RFA and MVD.⁵³ The occurrence rates of numbness following RFA were 40% and 18.7% at 3- and 12-months, respectively.¹⁷⁵ The same RCT found paresthesia was less frequent, occurring in no more than 13.3% and dropping to less than 7% after 12 months.

Patient Experience

Mansano, et al. found the RFA group reported greater improvement in HRQoL compared to sham intervention through 1 month follow-up.¹⁷⁵

Health Care Utilization

Li, et al. synthesized the findings of 9 non-randomized comparative studies and found there was no significant difference in postoperative medication use between groups receiving RFA or MVD.¹⁷⁷ Sozer, et al. reported that the time to second or third procedures and the time to relapse did not differ significantly between RFA, MVD, or gamma knife radiosurgery.⁵⁴ A small RCT indicated the mean reduction in anticonvulsant consumption was significantly greater in the RFA group at 1 month (84.75%) than in the sham-procedure group (16.46%).¹⁷⁵

Potential Effect Modifiers

Abduhamid, et al. compared RFA of the Gasserian ganglion and peripheral branches of the trigeminal nerve in terms of efficacy and rate of complications.⁵⁵ Data derived from 5 RCTs (N=239) demonstrated a non-significant trend for RFA of the peripheral nerve to have higher immediate pain reduction rates and higher recurrence rates. RFA of the Gasserian ganglion was associated with masticatory weakness, while RFA was associated with facial swelling and numbness of V2.

Wu, et al. summarized the effectiveness and safety of TN treatment via different RFA approaches (i.e., continuous radiofrequency ablation (CRFA), pulsed radiofrequency ablation (PRFA), and combined continuous and pulsed RFA (CCPRFA) techniques).⁵⁶ PRFA had no difference in pain relief in comparison with CRFA, while CRFA was more effective than CCPRFA (P<0.05). The comparison of complication rates showed that PRFA and CCPRFA were safer than CRFA.

A RCT compared the outcomes of patients with idiopathic TN who received either trigeminal ganglion radiofrequency thermocoagulation (TG-RFT) or maxillary/mandibular nerve diagnostic blocks and PRF procedures.⁵⁷ No statistical differences were found in pain and anticonvulsant use measures between the groups. Hypoesthesia occurred in 2 TG-RFT patients, and masseter weakness was observed in 1 patient, while no adverse events were reported in the PRF group.

Analysis of Evidence/Rationale for Decision Making

The evidence describing the efficacy/effectiveness of PNIs on pain associated with TN is very uncertain, as it is limited to results from 2 small retrospective case series (very low certainty evidence). There is low-certainty evidence that PNIs for individuals with TN may result in no serious adverse events. There is low-certainty evidence that suggests the addition of calcitonin to PNIs for the treatment of individuals with TN results in improved health outcomes. No evidence specific to PNIs was identified regarding measures of patient experience or health care utilization.

While robust literature is lacking, the overall evidence for RFT of the trigeminal nerve for TN was consistently favorable for refractory TN. In comparison to alternative procedures, the evidence supports that it was at least as safe and effective as the alternatives. Therefore, for refractory cases in which treatment options are limited, the use is considered reasonable and necessary.

L. Thoracic Nerve Blocks

Background

Thoracic nerve blocks are commonly used for anesthesia for surgical procedures. The role of these blocks in chronic pain management is being explored. Intercostal neuralgia is described as pain along the distribution of the intercostal nerve resulting in pain. It can be challenging to treat.¹⁷⁸

Coverage

Thoracic nerve blocks, including blocks of the intercostal nerve (INB) and erector spinae plane (ESP) for chronic pain management, are non-covered.

Thoracic Nerve Blocks

A single retrospective case-control study (N=39; mean age ~55 years) compared the observed effects of INB and ESP blocks in the treatment of PHN.¹⁷⁹ There was no significant difference between the groups in week 4 and week 12 pain scores. The scores for neuropathic pain and sleep interference at weeks 4 and 12 were significantly lower in the ESP group compared with the INB group. In addition to limitations imposed by the study design, there was no true control group. Additionally, the small size produced imprecise results, and there was very serious indirectness (single site, outside the USA, younger age than the U.S. Medicare population).

Thoracic Cryoneurolysis and RFA

A case report included 2 cases in which RFA was used to treat intercostal neuralgia successfully.¹⁷⁸

Analysis of Evidence/Rationale for Decision Making

The certainty of evidence is very low, limited only to a small number of cases, and it is uncertain if there is a benefit for thoracic nerve blocks or RFA for chronic pain of the intercostal nerve.

Peripheral Nerve Blocks (Multiple Nerves)

Eker, et al. ¹⁸⁰ conducted a single site RCT to evaluate the efficacy of methylprednisolone administered at the site of peripheral nerve injury for managing neuropathic pain. The study included 88 participants (mean age 54.8 years) with chronic neuropathic pain secondary to transection/compression, tension from painful scars, ischemia, accidental intraneural injection, repetitive microtrauma/entrapment, or surgical etiologies. Eligible patients had chronic (≥6 months) neuropathic pain, where daily intensity was reported as ≥ 5 on the 11-point NRS that was unresponsive to prior pharmacotherapy including NSAIDs, paracetamol and/or opioids. The intervention involved US-guided nerve injections with either 0.5% lidocaine or 80 mg methylprednisolone plus 0.5% lidocaine in a 10-20 ml solution (10 ml utilized for upper extremity injections and 20 ml utilized for the lower extremities). The intervention targeted 7 nerve types: suprascapular, thoracic paravertebral, femoral, common peroneal, sciatic, lateral distal sciatic, and popliteal.

Over a 3-month follow-up, the study assessed multiple outcomes, including pain intensity, neuropathic pain characteristics (assessed by the Leeds Assessment of Neuropathic Symptoms and Signs [LANSS] questionnaire), and post-intervention analgesic use. The methylprednisolone group demonstrated superior pain relief at 3-month follow-up. Both groups showed significant immediate post-injection pain reduction (P < 0.0001), but this did not persist at the 3-month follow-up. The methylprednisolone group maintained stable pain scores (post-injection: 2.0±1.4; 3-month: 2.0± 1.4, P > 0.05), while the lidocaine group regressed towards baseline. This resulted in a clinically significant between-group difference in pain at 3 months.

Neuropathic symptom improvement was significantly better with methylprednisolone, evidenced by greater reductions in LANSS scores (P < 0.0001), as well as resolution of numbness (95.4% vs 0%, P <0.001) burning sensation (100% vs 27%, P < 0.0001), hyperalgesia (96.4% vs 0%, P < 0.0001) and allodynia (100% vs 80.7%, P = 0.028). The active treatment also reduced analgesic use, with more patients discontinuing tramadol (31 vs 13) and lower mean daily consumption (22.7± 39.5 mg vs 97.7±76.2 mg, P < 0.0001).

Safety analysis revealed no serious adverse effects, with only minor transient side effects such as mild injection site discomfort, temporary numbness, a burning sensation, hyperalgesia, and allodynia.

The study was judged to have a high ROB due to uncertainties about the handling of missing data in the analysis. The generalizability of findings is limited by the single-center design, the small number of injections for heterogeneous nerve targets, and the inability to assess the discrete effects of specific PNIs. The certainty of evidence was rated as very low (serious study limitations, indirectness, and imprecision).

Anesthesia

The American Society of Anesthesiologists also provides guidelines for anesthetic care during interventional pain procedures for adults, stating that when sedation is provided during the performance of pain procedures, it is important that the patient can be responsive during critical portions of the procedure to report potential procedure-related paresthesia, acute changes in pain intensity, or function for potential toxicity. The committee opinion states that interventional pain procedures generally only require local anesthetic; however, patients may also elect to receive supplemental sedation, but they must remain conscious. Examples of procedures that typically do not require moderate sedation and/or an anesthesia care team include PNIs. They also state that significant patient anxiety, medical comorbidities, procedures that require the patient to remain motionless for prolonged periods of time or remain in a painful position may require moderate sedation or the anesthesia care team, and an example of such a procedure is RFA.¹

Contractor Advisory Meeting

A multijurisdictional CAC meeting was hosted on 2/3/25 by National Government Services (NGS), Palmetto GBA, CGS Administrators, WPS and Noridian Healthcare Solutions.

• The subject matter experts (SMEs) were favorable to the use of PNIs and RFA for genicular nerves after failed conservative measures, stating level I evidence. They acknowledge challenges in the literature, including short-term follow up, randomization issues, and variables in outcome measures; however, they indicated SR/MA supported overall improvements. They stated a lack of societal support or guidelines. They explained that there is a lack of evidence to set a threshold for diagnostic injections to predict response to RFA and that many perform RFA without diagnostic injections. There was agreement that there is a lack of evidence to state whether RFA or cryoneurolysis is superior.
• The SMEs felt there was little role for intercostal blocks outside of anesthesia.
• The SMEs stated ganglion repair blocks for coccydynia are rarely used and not well studied.
• They discussed limited evidence for the use of pudendal nerve blocks for chronic pelvic pain.
• The SMEs stated there is evidence to support the use of corticosteroid injections for CTS for short term use. They stated there is no evidence for acute (<6 weeks) or long-term use. They explained there is a lack of evidence on the number of times an injection can be repeated safely. Evidence for ultrasound use with CTS was variable.
• A SME explained that conservative measures should be used before injections for occipital neuralgia, but there is evidence to support use for refractory headache. They explained it is supported by the American Academy of Neurology (however, we were not able to locate any guidelines or statements).
• SMEs stated there is limited evidence to support the use of SGB for spasticity, but not hot flashes, post-traumatic stress syndrome or Bell’s palsy. SMEs advocate a role for blocks in refractory chronic pain when they have difficulty participating in PT/OT.
• The SMEs explained that RFA for TN is a mainstay of treatment for refractory TN and can avoid surgery for many patients with low risk. Evidence to support frequency is limited.

GRADE certainty of evidence classification scheme

Source: Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook.

GRADE Domains

ACIP GRADE Handbook for Developing Evidence-based Recommendations: Formulating questions, conducting the systematic review, and assessing the certainty of the evidence using GRADE. Chapter 8: Domains Decreasing Certainty in the Evidence. Updated April 22, 2024; U.S. Centers of Disease Control and Prevention: ACIP GRADE Handbook

TABLES

Table A: Stellate Ganglion Nerve Block: Characteristics of Included Studies

6MWT = 6-minute walking test; CSI = central sensitization inventory; GNB = genicular nerve block; GPES = global perceived effect scale; HEP = home exercise program; HRQL = health-related quality of life; IACSI = intra-articular corticosteroid injection; ICOAP = intermittent and constant osteoarthritis pain scale; KOA = knee osteoarthritis; LANSS = Leeds assessment of neuropathic symptoms and signs; MQS = Medication quantification scale; NHP = Nottingham health profile; NRS = numeric rating scale; OKS = Oxford knee score; QAQ = quantitative analgesic questionnaire; QMA = quadriceps muscle cross-sectional area; QoL = quality of life; RCT = randomized controlled trial; RFA = radiofrequency ablation; RoB = risk of bias; SF-12 = short-from 12; ULS = ultrasound; VAS = visual analog scale; VNRS = verbal numeric rating scale; WOMAC = Western Ontario McMaster Universities Osteoarthritis Index; SAH: Subarachnoid hemorrhage; aSAH: Aneurysmal subarachnoid hemorrhage; EBI: Early brain injury; SGB: Stellate Ganglion Block; EBI: Early Brain Injury; MCA: Middle cerebral artery; BA: Basilar artery; Vm: Mean cerebral blood flow velocity; CVS: Cerebral vasospasm; CBF: Cerebral blood flow; BBB: Blood-brain barrier; CT: Computed tomography; TCD: Transcranial doppler; IL-1β: Interleukin-1β; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor alpha; ET-1: Endothelin-1; NPY: Neuropeptide; S100β: S100βprotein; NSE: Neuron specific enolase; GOS: Glasgow Outcome score; H: Hunt-Hess; WFNS: World Federation of Neurological Surgeons; ACoA: Anterior communicating artery; ACA: Anterior cerebral artery; MCA: Middle cerebral artery; PICA: Posterior inferior cerebellar artery; BA: Basilar artery; PCoA: Posterior communicating artery; CN: Cranial nerve; POSD, postoperative sleep disturbance; PSQI, Pittsburgh Sleep Quality Index; surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10); ACA = anterior cerebral artery; AE = adverse event; aSAH = aneurysmal subarachnoid hemorrhage; CBFV = cerebral blood flow velocity; CTP = CT perfusion; CVS = cerebral vasospasm; DCI = delayed cerebral ischemia; EBI = early brain injury; ICA = internal carotid artery; ICP = intracranial pressure; MCA = middle cerebral artery; mRS = modified Rankin Scale; SGB = stellate ganglion block; TCD = transcranial Doppler. Blood flow velocity of arteries such as vertebrobasilar arteries (VA-BA), middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA) of the two groups of subjects were detected through the occipital window and the temporal window. After computer processing, pulse index (PI), resistance index (RI), and average blood flow velocity (Vm).

Table B: Stellate Ganglion Nerve Block: Findings of Included Studies

NRS: numeric rating scale; MQS III: Medication Quantification Scale version III; CBZ: carbamazepine; PRG: pregabalin; GBP: gabapentin; TRMD: tramadol; test st: test statistic; SD: standard deviation; MW: masseter weakness; Group RFT: trigeminal ganglion radiofrequency thermocoagulation group; Group PRF: maxillary or mandibular (max/mand) nerve pulsed radiofrequency group; TN = trigeminal neuralgia; MS = multiple sclerosis; CRF = continuous radiofrequency; BNI = Barrow Neurological Institute; ITT = intention to treat; PP = per protocol; BC = balloon compression; GR = glycerol rhizolysis; RF= radiofrequency ablation.

Table C: Ganglion Impar Blocks: Characteristics of Studies

GIB = ganglion Impar block; ESWT = extracorporeal shockwave therapy; NSAIDs = nonsteroidal anti-inflammatory drugs; RFA = radiofrequency ablation

Table D: Ganglion Impar Blocks: Findings of included studies

CI = confidence interval; GIB = ganglion Impar block; NRS = numeric rating scale; NRSI = non-randomized study of an intervention; ODI = Oswestry disability index; PGIC = perceived global impression of change; RCT = randomized controlled trial; RFA = radiofrequency ablation; ROB = risk of bias; SR = systematic review; VAS = visual analog scale

Table E: Genicular Nerve Injections: Characteristics of randomized controlled trials

f/u = follow-up; GNB = genicular nerve block; HEP = home exercise program; IACSI = intra-articular corticosteroid injection; K-L = Kellgren-Lawrence; KOA = knee osteoarthritis; N/A = not applicable; RFA = radiofrequency ablation; TENS = transcutaneous nerve stimulation; ULS = ultrasound

Table F: Genicular Nerve Injections: Findings of randomized controlled trials

6MWT = 6-minute walk test; GNA = genicular nerve ablation; GNB = genicular nerve block; GPE = global perceived effect; HEP = home exercise plan; HRQoL = health-related quality of life; ICOAP = intermittent and constant osteoarthritis pain scale; KSS = Knee Society Score; LANSS = Leeds assessment of neuropathic symptoms and signs; NHP = Nottingham health profile; NRS = numeric rating scale; OKS = Oxford knee score; RFA = radiofrequency ablation; ROB = risk of bias; QAQ = quantitative analgesic questionnaire; VAS = visual analog scale; WOMAC = Western Ontario McMaster Universities Osteoarthritis Index

Table G: Occipital Nerve Block: Characteristics of Included Studies

HRQL = health-related quality of life; IACSI = intra-articular corticosteroid injection; NRS = numeric rating scale; QoL = quality of life; RCT = randomized controlled trial; RFA = radiofrequency ablation; RoB = risk of bias; SF-12 = short-from 12; ULS = ultrasound; VAS = visual analog scale; CM = Chronic migraine; GONB = Greater occipital nerve block.

Table H: Occipital Nerve Block: Findings of Included Studies

Table I: Suprascapular Nerve Block: Characteristics of Included Studies

AC = adhesive capsulitis; IAI = intra-articular corticosteroid injection; SSNB= suprascapular nerve block; ROM = range of motion; SPADI = Shoulder Pain and Disability Index; NRS = Numeric Rating Scale; ROMs = Range of Motion; SF-36 = Short Form 36; NRS = Numeric Rating Scale; AEs = Adverse events; HAQ = Health Assessment Questionnaire; LMG = landmark‑guided; SOC = standard of care; MCID = minimum clinically important difference.

Table J: Suprascapular Nerve Block: Findings of Included Studies

Table K: Radiofrequency Ablation for Trigeminal Neuralgia: Characteristics of Included Studies

BC = balloon compression; GR = glycerol rhizotomy; MS = multiple sclerosis; MVD = microvascular decompression; NRSI = non-randomized study(ies) of an intervention; RCT = randomized controlled trial; RFA = radiofrequency ablation; TN = trigeminal neuralgia

Table L: Radiofrequency Ablation for Trigeminal Neuralgia: Findings of Included Studies

BC = balloon compression; CI = confidence interval; CCPRFA = combined continuous and pulsed radiofrequency ablation; CRFA = continuous radiofrequency ablation; F/U = follow-up; GKRS = gamma knife radiosurgery; GR = glycerol rhizotomy/rhizolysis; HRQoL = health-related quality of life; MQS III = medication quantification scale version 3; MS = multiple sclerosis; MVD = microvascular decompression; NRSI = non-randomized study of an intervention; OR = odds ratio; PRFA = pulsed radiofrequency ablation; RCT = randomized controlled trial; RFA = radiofrequency ablation; RFT = radiofrequency thermoablation; ROB = risk of bias; RR = relative risk; SR = systematic review; SR/MA = systematic review/meta-analysis; TN = trigeminal neuralgia

Associated LCDs

L39128 Amniotic and Placental-Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound

L38745 Platelet Rich Plasma

L39836 Botulinum Toxin Injections

L39671 Trigger Point Injections (TPI)

L38994 Epidural Steroid Injections for Pain Management

L39402 Sacroiliac Joint Injections and Procedures

L39797 Minimally Invasive Arthrodesis of the Sacroiliac Joint (SIJ)

L38765 Facet Joint Interventions for Pain Management

N/A

1. American Society of Anesthesiologists. Committee on Pain Medicine. Statement on Anesthetic Care During Interventional Pain Procedures for Adults. Published 2021. Updated 10/13/21. Accessed 7/20/26.
2. Munirama S, McLeod G. A systematic review and meta-analysis of ultrasound versus electrical stimulation for peripheral nerve location and blockade. Anaesthesia. 2015;70(9):1084-1091. doi:10.1111/anae.13128.
3. Rikard SM, Strahan AE, Schmit KM, Guy GP Jr. Chronic pain among adults — United States, 2019–2021. MMWR Morb Mortal Wkly Rep. 2023;72(15):379–385. doi:10.15585/mmwr.mm7215a1.
4. National Institutes of Health, National Center for Complementary and Integrative Health. Pain. Accessed 7/20/26.
5. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021;397(10289):2082-2097. doi:10.1016/S0140-6736(21)00393-7.
6. Pitcher MH, Von Korff M, Bushnell MC, Porter L. Prevalence and profile of high-impact chronic pain in the United States. J Pain. 2019;20(2):146-160. doi:10.1016/j.jpain.2018.07.006.
7. Thomas KH, Dalili MN, Cheng HY, et al. Prevalence of problematic pharmaceutical opioid use in patients with chronic non-cancer pain: A systematic review and meta-analysis. Addiction. 2024;119(11):1904-1922. doi:10.1111/add.16616.
8. De La Rosa JS, Brady BR, Ibrahim MM, et al. Co-occurrence of chronic pain and anxiety/depression symptoms in U.S. adults: prevalence, functional impacts, and opportunities. Pain. 2024;165(3):666-673. doi:10.1097/j.pain.0000000000003056.
9. De La Rosa JS, Brady BR, Herder KE, et al. The unmet mental health needs of U.S. adults living with chronic pain. Pain. 2024;165(12):2877-2887. doi:10.1097/j.pain.0000000000003340.
10. Lucas JW, Sohi I. Chronic pain and high-impact chronic pain in U.S. adults, 2023. NCHS Data Brief.2024;(518):CS355235. doi:10.15620/cdc/169630.
11. Bouhassira D. Neuropathic pain: Definition, assessment and epidemiology. Rev Neurol (Paris). 2019;175(1-2):16-25. doi:10.1016/j.neurol.2018.09.016.
12. Moisset X. Neuropathic pain: Evidence based recommendations. Presse Med. 2024;53(2):104232. doi:10.1016/j.lpm.2024.104232.
13. Ori A, Jindal A, Nwazota N, Pearson ACS, Yalamuru B. Peripheral nerve injections. Phys Med Rehabil Clin N Am. 2022;33(2):489-517. doi:10.1016/j.pmr.2022.02.004.
14. Ashworth NL, Bland JDP, Chapman KM, Tardif G, Albarqouni L, Nagendran A. Local corticosteroid injection versus placebo for carpal tunnel syndrome. Cochrane Database Syst Rev. 2023;2(2):CD015148. doi:10.1002/14651858.CD015148.
15. Hofer M, Ranstam J, Atroshi I. Extended follow-up of local steroid injection for carpal tunnel syndrome: A randomized clinical trial. JAMA Netw Open. 2021;4(10):e2130753. doi:10.1001/jamanetworkopen.2021.30753.
16. Karjalainen TV, Lusa V, Page MJ, O'Connor D, Massy-Westropp N, Peters SE. Splinting for carpal tunnel syndrome. Cochrane Database Syst Rev. 2023;2(2):CD010003. Published 2023 Feb 27. doi:10.1002/14651858.CD010003.pub2.
17. Lusa V, Karjalainen TV, Pääkkönen M, Rajamäki TJ, Jaatinen K. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2024;1(1):CD001552. Published 2024 Jan 8. doi:10.1002/14651858.CD001552.pub3.
18. Jenkins PJ, Duckworth AD, Watts AC, McEachan JE. Corticosteroid injection for carpal tunnel syndrome: a 5-year survivorship analysis. Hand (N Y). 2012;7(2):151-156. doi:10.1007/s11552-012-9390-8.
19. Atroshi I, Flondell M, Hofer M, Ranstam J. Methylprednisolone injections for the carpal tunnel syndrome: a randomized, placebo-controlled trial. Ann Intern Med. 2013;159(5):309-317. doi:10.7326/0003-4819-159-5-201309030-00004.
20. Chesterton LS, Dziedzic KS, van der Windt DA, et al. The clinical and cost effectiveness of steroid injection compared with night splints for carpal tunnel syndrome: the INSTINCTS randomised clinical trial study protocol. BMC Musculoskelet Disord. 2016;17(1):415. doi:10.1186/s12891-016-1264-8.
21. Burton C, Rathod-Mistry T, Blackburn S, et al. The effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome: 24-month follow-up of a randomized trial. Rheumatology (Oxford). 2023;62(2):546-554. doi:10.1093/rheumatology/keac219.
22. Yang FA, Shih YC, Hong JP, Wu CW, Liao CD, Chen HC. Ultrasound-guided corticosteroid injection for patients with carpal tunnel syndrome: a systematic review and meta-analysis of randomized controlled trials. Sci Rep. 2021;11(1):10417. doi:10.1038/s41598-021-89898-7.
23. Graham B, Peljovich AE, Afra R, et al. The American Academy of Orthopaedic Surgeons Evidence-Based Clinical Practice Guideline on: Management of Carpal Tunnel Syndrome. J Bone Joint Surg Am. 2016;98(20):1750-1754. doi:10.2106/JBJS.16.00719.
24. Huisstede BM, Fridén J, Coert JH, Hoogvliet P; European HANDGUIDE Group. Carpal tunnel syndrome: hand surgeons, hand therapists, and physical medicine and rehabilitation physicians agree on a multidisciplinary treatment guideline—results from the European HANDGUIDE Study. Arch Phys Med Rehabil. 2014;95(12):2253-2263. doi:10.1016/j.apmr.2014.06.022.
25. Taylor SS, Noor N, Urits I. et al. Complex regional pain syndrome: A comprehensive review. Pain Ther. 2021;10(2):875–892. doi.org/10.1007/s40122-021-00279-4.
26. Harden RN, McCabe CS, Goebel A, et al. Complex regional pain syndrome: Practical diagnostic and treatment guidelines, 5th Edition. Pain Med. 2022;23(Suppl 1):S1-S53. org/10.1093/pm/pnac046.
27. Datta R, Agrawal J, Sharma A, Rathore VS, Datta S. A study of the efficacy of stellate ganglion blocks in complex regional pain syndromes of the upper body. J Anaesthesiol Clin Pharmacol. 2017;33(4):534-540. doi:10.4103/joacp.JOACP_326_16.
28. Tian Y, Hu Y, Hu T, et al. Stellate ganglion block therapy for complex regional pain syndrome: A systematic review and meta-analysis. Pain Physician. 2024;27(4):175-184.
29. O'Connell NE, Wand BM, Gibson W, Carr DB, Birklein F, Stanton TR. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2016;7(7):CD004598. doi:10.1002/14651858.CD004598.pub4.
30. Ferraro MC, Cashin AG, Wand BM, et al. Interventions for treating pain and disability in adults with complex regional pain syndrome: an overview of systematic reviews. Cochrane Database Syst Rev. 2023;6(6):CD009416. doi:10.1002/14651858.CD009416.pub3.
31. Wang C, Yuan F, Cai L, Lu H, Chen G, Zhou J. Ultrasound-guided stellate ganglion block combined with extracorporeal shock wave therapy on postherpetic neuralgia. J Healthc Eng. 2022;2022:9808994. doi:10.1155/2022/9808994.
32. Rae Olmsted KL, Bartoszek M, Mulvaney S, et al. Effect of stellate ganglion block treatment on posttraumatic stress disorder symptoms: A randomized clinical trial [published correction appears in JAMA Psychiatry. 2020 Feb 1;77(2):218. doi: 10.1001/jamapsychiatry.2019.4511.] [published correction appears in JAMA Psychiatry. 2020 Sep 1;77(9):982. doi: 10.1001/jamapsychiatry.2020.1829.]. JAMA Psychiatry. 2020;77(2):130-138. doi:10.1001/jamapsychiatry.2019.3474.
33. Yoo Y, Lee CS, Kim YC, Moon JY, Finlayson RJ. A randomized comparison between 4, 6 and 8 mL of local anesthetic for ultrasound-guided stellate ganglion block. J Clin Med. 2019;8(9):1314. doi:10.3390/jcm8091314.
34. Ito N, Umazume M, Ojima Y, et al. Comparison of traditional two-injection dorsal digital block versus transthecal and subcutaneous single-injection digital block: A systematic review and meta-analysis. Hand Surg Rehabil. 2021;40(4):369-376. doi:10.1016/j.hansur.2021.04.004.
35. Elsaman AM, Hamed A, Radwan AR. Therapeutic potential of digital nerve block in rheumatoid arthritis patients: A clinical and sonographic prospective study. Clin J Pain. 2021;37(6):413-420. doi:10.1097/AJP.0000000000000935.
36. Andersen GØ, Milosevic S, Jensen MM, et al. Coccydynia-The efficacy of available treatment options: A systematic review. Global Spine J. 2022;12(7):1611-1623. doi:10.1177/21925682211065389.
37. Choudhary R, Kunal K, Kumar D, Nagaraju V, Verma S. Improvement in pain following ganglion impar blocks and radiofrequency ablation in coccygodynia patients: A systematic review. Rev Bras Ortop (Sao Paulo). 2021;56(5):558-566. doi:10.1055/s-0041-1735829.
38. Mazzoleni MG, Maffulli N, Bardazzi T, Memminger M, Bertini FA, Migliorini F. Management of coccygodynia: talking points from a systematic review of recent clinical trials. Ann Jt. 2025;10:9. Published 2025 Jan 21. doi:10.21037/aoj-24-40.
39. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. doi:10.1136/bmj.j4008.
40. Jevotovsky DS, Chopra H, Pak DJ, et al. Non-neurodestructive ganglion impar blocks for coccydynia and related disorders: a systematic review and meta-analysis. Reg Anesth Pain Med. 2025;50(11):845-857.
41. Malhotra N, Phogat V, Sinha N, Kumar A, Charan N, Arun. Comparison of radiofrequency thermocoagulation of ganglion Impar with block using a combination of local anaesthetic and steroid in chronic perineal pain. J Anaesthesiol Clin Pharmacol. 2025;41(2):280-285. doi:10.4103/joacp.joacp_40_24.
42. Sagir O, Demir HF, Ugun F, Atik B. Retrospective evaluation of pain in patients with coccydynia who underwent impar ganglion block. BMC Anesthesiol. 2020;20(1):110. doi:10.1186/s12871-020-01034-6.
43. Sir E, Eksert S. Comparison of block and pulsed radiofrequency of the ganglion impar in coccygodynia. Turk J Med Sci. 2019;49(5):1555-1559. doi:10.3906/sag-1906-51.
44. Le Clerc Q-C, Riant T, Levesque A, et al. Repeated ganglion impar block in a cohort of 83 patients with chronic pelvic and perineal pain. Pain Physician. 2017;20:E823-E828.
45. Genc Perdecioglu GR, Yildiz G. Coccygeal nerve blockade vs. Impar ganglion blockade in coccydynia: A randomised clinical trial. Cureus. 2024;16(9):e69118. doi:10.7759/cureus.69118.
46. Govardhani Y, RamMohan G, Abhijith S, Savithri B. A comparative retrospective study of the efficacy of caudal epidural with manipulation versus ganglion impar block with manipulation in patients with coccydynia. Indian Journal of Pain. 2021;35(1):42-45. doi:4103/ijpn.ijpn_152_20.
47. Malhotra N, Goyal S, Kumar A, Kanika, Singla V, Kundu ZS. Comparative evaluation of transsacrococcygeal and transcoccygeal approach of ganglion impar block for management of coccygodynia. J Anaesthesiol Clin Pharmacol. 2021;37(1):90-96. doi:10.4103/joacp.JOACP_588_20.
48. Conger A, Gililland J, Anderson L, Pelt CE, Peters C, McCormick ZL. Genicular nerve radiofrequency ablation for the treatment of painful knee osteoarthritis: current evidence and future directions. Pain Med. 2021;22(Suppl 1):S20-S23. doi:10.1093/pm/pnab129.
49. Fonkoue L, Behets CW, Steyaert A, et al. Accuracy of fluoroscopic-guided genicular nerve blockade: a need for revisiting anatomical landmarks. Reg Anesth Pain Med. 2019;44(10):950-958. doi:10.1136/rapm-2019-100451.
50. Kidd VD, Strum SR, Strum DS, Shah J. Genicular nerve radiofrequency ablation for painful knee arthritis: the why and the how. JBJS Essent Surg Tech. 2019;9(1):e10. doi:10.2106/JBJS.ST.18.00016.
51. Cosman Jr ER, Dolensky JR, Hoffman RA. Factors that affect radiofrequency heat lesion size. Pain Medicine. 2014;15(12):2020–2036. doi.org/10.1111/pme.12566.
52. Yan C, Zhang Q, Liu C, et al. Efficacy and safety of radiofrequency in the treatment of trigeminal neuralgia: a systematic review and meta-analysis. Acta Neurol Belg. 2022;122(4):1019-1030. doi:10.1007/s13760-021-01654-w.
53. Habib HA, Ellakany MH, Elnoamany H, Elnaggar AG. Microvascular decompression versus radiofrequency ablation in trigeminal neuralgia of the maxillary and mandibular divisions. Asian J Neurosurg. 2024;19(2):221-227. doi:10.1055/s-0044-1779516.
54. Sozer A, Kale A, Karaaslan B, et al. Multimodal treatment of multiple sclerosis related trigeminal neuralgia: A single centre experience. Mult Scler Relat Disord. 2025;99:106508. doi:10.1016/j.msard.2025.106508.
55. Abduhamid AS, Alomari MS, Ghaddaf AA, et al. Radiofrequency thermoablation of the peripheral branches of trigeminal nerve versus the Gasserian ganglion for treating idiopathic trigeminal neuralgia: A systematic review and meta-analysis. J Clin Neurosci. 2022;104:42-47. doi:10.1016/j.jocn.2022.08.005.
56. Wu H, Zhou J, Chen J, Gu Y, Shi L, Ni H. Therapeutic efficacy and safety of radiofrequency ablation for the treatment of trigeminal neuralgia: a systematic review and meta-analysis. J Pain Res. 2019;12:423-441. doi:10.2147/JPR.S176960.
57. Yildiz G, Akkaya OT. A comparison between the efficacy of trigeminal ganglion radiofrequency thermocoagulation and ultrasound-guided maxillary-mandibular nerve pulsed radiofrequency in the treatment of trigeminal neuralgia: A randomized clinical trial. Cureus. 2024;16(6):e61565. doi:10.7759/cureus.61565.
58. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578-1589. doi:10.1016/j.joca.2019.06.011.
59. Ghai A, Kaushik T, Kundu ZS, Wadhera S, Wadhera R. Evaluation of new approach to ultrasound guided stellate ganglion block. Saudi J Anaesth. 2016;10(2):161-167. doi:10.4103/1658-354X.168815.
60. American Academy of Orthopaedic Surgeons. Management of Osteoarthritis of the Knee (Non-Arthroplasty) Evidence-Based Clinical Practice Guideline. Accessed 7/20/26.
61. Makkar JK, Warrier G, Ghai B, et al. Effect of radiofrequency ablation of genicular nerves on the isokinetic muscle strength of knee joint in patients with osteoarthritis knee: a randomized double-blind sham controlled clinical trial. Pain Medicine. 2024;25(12):738-748. doi.org/10.1093/pm/pnae077.
62. Fogarty AE, Burnham T, Kuo K, et al. The effectiveness of fluoroscopically guided genicular nerve radiofrequency ablation for the treatment of chronic knee pain due to osteoarthritis: A systematic review. Am J Phys Med Rehabil. 2022;101(5):482-492. doi:10.1097/PHM.0000000000001813.
63. Nygaard NPB, Koch-Jensen C, Vaegter HB, Wedderkopp N, Blichfeldt-Eckhardt M, Gram B. Efficacy of cryoneurolysis on chronic pain in patients with knee osteoarthritis: A double-blinded randomized controlled sham trial. Anesthesiology. 2025;142(6):1114-1126. doi:10.1097/ALN.0000000000005396.
64. McCormick ZL, Reddy R, Korn M, et al. A prospective randomized trial of prognostic genicular nerve blocks to determine the predictive value for the outcome of cooled radiofrequency ablation for chronic knee pain due to osteoarthritis. Pain Med. 2018;19(8):1628-1638. doi:10.1093/pm/pnx286.
65. Radnovich R, Scott D, Patel AT, et al. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthritis Cartilage. 2017;25(8):1247-1256. doi:10.1016/j.joca.2017.03.006.
66. Iannaccone F, Dixon S, Kaufman A. A review of long-term pain relief after genicular nerve radiofrequency ablation in chronic knee osteoarthritis. Pain Physician. 2017;20(3):E437-E444.
67. Meiling JB, Barndt BS, Ha CT, et al. The therapeutic effect of genicular nerve radiofrequency for chronic knee pain after a total knee arthroplasty: A systematic review. Interv Pain Med. 2022;1(1):100072. doi:10.1016/j.inpm.2022.100072.
68. Almeida M, Saragiotto BT, Hunter DJ, et al. Efficacy and safety of minimally invasive interventions targeting the genicular nerves for knee osteoarthritis: A meta-analysis. Osteoarthritis Cartilage. 2025;33(5):535-547. doi:10.1016/j.joca.2025.02.780.
69. Manes TJ, Walker J, Ricken R, et al. Cryoneurolysis is a safe and effective method for reducing perioperative pain in total knee arthroplasty. J Orthopaedic Experience & Innovation. 2024;5(2). org/10.60118/001c.122460.
70. Li W, Xu F, Chen F, Cao L, Bao X. Effect of genicular nerve block (GNB) on pain in lesions of the knee joint: A meta-analysis of randomized controlled trials. J Pain Res. 2025;18:511-522. doi:10.2147/JPR.S503937.
71. Vilchez-Cavazos F, Gamboa Alonso AA, Simental-Mendia M, Pena-Martinez VM, Acosta-Olivo CA, Villarreal-Villarreal GA. Genicular nerve block for knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials. Clin J Pain. 2024;40(10):618-624. doi:10.1097/AJP.0000000000001240.
72. Tan YL, Neo EJR, Wee TC. Ultrasound-guided genicular nerve blockade with pharmacological agents for chronic knee osteoarthritis: A systematic review. Pain Physician. 2022;25(4):E489-E502.
73. Ghai B, Kumar M, Makkar JK, Goni V. Comparison of ultrasound guided pulsed radiofrequency of genicular nerve with local anesthetic and steroid block for management of osteoarthritis knee pain. Korean J Pain. 2022;35(2):183-190. doi:10.3344/kjp.2022.35.2.183.
74. Rathore R, Joshi M, Saharan A, Agrawal H. Effect of ultrasound-guided genicular nerve block in knee osteoarthritis with neuropathic pain. Indian Journal of Physical Medicine & Rehabilitation. 2022;32(2):72-8. doi:10.4103/ijpmr.ijpmr_9_22.
75. Reysner M, Reysner T, Kowalski G, Mularski A, Daroszewski P, Wieczorowska-Tobis K. Effect of ultrasound-guided genicular nerve neurolysis versus sham procedure on pain in patients with knee osteoarthritis: a randomized clinical trial. Pain Med. 2026;27(1):33-42. doi:10.1093/pm/pnaf081.
76. Shanahan EM, Robinson L, Lyne S, et al. Genicular nerve block for pain management in patients with knee osteoarthritis: A randomized placebo-controlled trial. Arthritis Rheumatol. 2023;75(2):201-209. doi:10.1002/art.42384.
77. Qudsi-Sinclair S, Borrás-Rubio E, Abellan-Guillén JF, Padilla Del Rey ML, Ruiz-Merino G. A comparison of genicular nerve treatment using either radiofrequency or analgesic block with corticosteroid for pain after a total knee arthroplasty: A double-blind, randomized clinical study. Pain Pract. 2017;17(5):578-588. doi:10.1111/papr.12481.
78. Güler T, Yurdakul FG, Onder ME, et al. Ultrasound-guided genicular nerve block versus physical therapy for chronic knee osteoarthritis: a prospective randomised study. Rheumatol Int. 2022;42(4):591-600. doi:10.1007/s00296-022-05101-8.
79. Elashmawy MM, Shabana AAH, Elsaid TO, Elhawary GM. Ultrasound-guided genicular nerve block versus alcoholic neurolysis for treatment of advanced knee osteoarthritis patients. The Egyptian Rheumatologist.2022;44(4):307-311. doi:10.1016/j.ejr.2022.04.002.
80. Cankurtaran D, Karaahmet OZ, Yildiz SY, Eksioglu E, Dulgeroglu D, Unlu E. Comparing the effectiveness of ultrasound guided versus blind genicular nerve block on pain, muscle strength with isokinetic device, physical function and quality of life in chronic knee osteoarthritis: A prospective randomized controlled study. Korean J. Pain. 2020;33(3):258-266. doi:10.3344/kjp.2020.33.3.258.
81. Kim D-H, Lee M-S, Lee S, Yoon S-H, Shin J-W, Choi S-S. A prospective randomized comparison of the efficacy of ultrasound- vs fluoroscopy-guided genicular nerve block for chronic knee osteoarthritis. Pain Physician. 2019;22(2):139-146.
82. Fonkoue L, Steyaert A, Kouame JEK, et al. A comparison of genicular nerve blockade with corticosteroids using either classical anatomical targets vs revised targets for pain and function in knee osteoarthritis: A double-blind, randomized controlled trial. Pain Med. 2021;22(5):1116-1126. doi:10.1093/pm/pnab014.
83. Orlić Karbić V. Sustic A. Therapeutic genicular nerve block for chronic pain management in patients with knee osteoarthritis. Acta Clin Croat. 2023;62(Suppl 4):34-39. doi: 10.20471/acc.2023.62.s4.5.
84. Ramalho RC, Fernandes TD, Peraro FF, Pugliese GM, Arliani GG, Ferreira GF. Ultrasound-guided genicular nerve block for knee osteoarthritis: A case series. Acta Ortop Bras. 2024;32(3):e277781. doi:10.1590/1413-785220243203e277781.
85. Chen B, Yang Y, Wang H, Guo X, Wu Z, Lan Z. Is radiofrequency ablation effective in treating patients with chronic knee osteoarthritis? A meta-analysis of randomized controlled trials. Ann Med Surg(Lond). 2023;86(1):412-420. doi:10.1097/MS9.0000000000001509.
86. Copay AG, Eyberg B, Chung AS, Zurcher KS, Chutkan N, Spangehl MJ. Minimum clinically important difference: Current trends in the orthopaedic literature, Part II: Lower extremity: A systematic review. JBJS Rev. 2018;6(9):e2. doi:10.2106/JBJS.RVW.17.00160.
87. Lee L, Epelboym Y. Review of genicular artery embolization, radiofrequency ablation, and cryoneurolysis in the management of osteoarthritis-related knee pain. Diagn Interv Radiol. 2023;29(4):614-620. doi:10.4274/dir.2022.221288.
88. Das G, Singam A, Chakole V, Das S, Sharma V. Efficacy and safety of cryoablation compared with cooled radiofrequency ablation of genicular nerves in advanced osteoarthritis of the knee: a study protocol of single-centric, assessor-blinded, randomized, parallel-group, non-inferiority study. Cardiovasc Intervent Radiol. 2024;47(4):508–514. doi.org/10.1007/s00270-024-03703-2.
89. Silva MDC, Perriman DM, Fearon AM, Couldrick JM, Scarvell JM. Minimal important change and difference for knee osteoarthritis outcome measurement tools after non-surgical interventions: a systematic review. BMJ Open. 2023;13(5):e063026. doi:10.1136/bmjopen-2022-063026.
90. Ma Y, Chen YS, Liu B, Sima L. Ultrasound-guided radiofrequency ablation for chronic osteoarthritis knee pain in the elderly: A randomized controlled trial. Pain Physician. 2024;27(3):121-128.
91. Chen AF, Khalouf F, Zora K, et al. Cooled radiofrequency ablation provides extended clinical utility in the management of knee osteoarthritis: 12-month results from a prospective, multi-center, randomized, cross-over trial comparing cooled radiofrequency ablation to a single hyaluronic acid injection. BMC Musculoskelet Disord. 2020;21(1):363. doi:10.1186/s12891-020-03380-5.
92. Chen AF, Khalouf F, Zora K, et al. Cooled radiofrequency ablation compared with a single injection of hyaluronic acid for chronic knee pain: A multicenter, randomized clinical trial demonstrating greater efficacy and equivalent safety for cooled radiofrequency ablation. J Bone Joint Surg Am. 2020;102(17):1501-1510. doi:10.2106/JBJS.19.00935.
93. Davis T, Loudermilk E, DePalma M, et al. Prospective, multicenter, randomized, crossover clinical trial comparing the safety and effectiveness of cooled radiofrequency ablation with corticosteroid injection in the management of knee pain from osteoarthritis. Reg Anesth Pain Med. 2018;43(1):84-91. doi:10.1097/AAP.0000000000000690.
94. Davis T, Loudermilk E, DePalma M, et al. Twelve-month analgesia and rescue, by cooled radiofrequency ablation treatment of osteoarthritic knee pain: results from a prospective, multicenter, randomized, cross-over trial. Reg Anesth Pain Med. 2019;44(4):499-506. doi:10.1136/rapm-2018-100051.
95. Vanneste T, Belba A, Kallewaard JW, et al. Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial). Reg Anesth Pain Med. 2023;48(5):197-204. doi:10.1136/rapm-2022-104054.
96. Belba A, Vanneste T, Kallewaard JW, et al. Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial. Reg Anesth Pain Med. 2025;50(1):36-45. doi:10.1136/rapm-2023-105127.
97. Kapural L, Minerali A, Sanders M, Matea M, Dua S. Cooled radiofrequency ablation provides prolonged pain relief compared to traditional radiofrequency ablation: A real-world, large retrospective clinical comparison from a single practice. J Pain Res. 2022;15:2577-2586. doi:10.2147/JPR.S373877.
98. Santana-Pineda MM, Vanlinthout LE, Santana-Ramírez S, Vanneste T, Van Zundert J, Novalbos-Ruiz JP. A randomized controlled trial to compare analgesia and functional improvement after continuous neuroablative and pulsed neuromodulative radiofrequency treatment of the genicular nerves in patients with knee osteoarthritis up to one year after the intervention. Pain Med. 2021;22(3):637-652. doi:10.1093/pm/pnaa309.
99. Chou SH, Shen PC, Lu CC, et al. Comparison of efficacy among three radiofrequency ablation techniques for treating knee osteoarthritis: A systematic review and meta-analysis. Int J Environ Res Public Health. 2021;18(14):7424. doi:10.3390/ijerph18147424.
100. Mohamed OS, Omar SM, Gaber AF, Hassanien MM, Mohamed AEM. Three needles approach-a new technique of genicular nerves radiofrequency ablation for pain relief in advanced chronic knee osteoarthritis: A randomized trial. Pain Physician. 2021;24(7):E1067-E1074.
101. Mont MA, Lin JH, Spitzer AI, et al. Improved pain and function with triamcinolone acetonide extended-release and cryoneurolysis for knee osteoarthritis: Use of a new real-world registry. J Arthroplasty. 2025;40(2):328-338.e2. doi:10.1016/j.arth.2024.06.055.
102. Protzman NM, Gyi J, Malhotra AD, Kooch JE. Examining the feasibility of radiofrequency treatment for chronic knee pain after total knee arthroplasty. PM&R. 2014;6(4):373-376. doi:10.1016/j.pmrj.2013.10.003.
103. Clendenen S, Greengrass R, Whalen J, O'Connor MI. Infrapatellar saphenous neuralgia after TKA can be improved with ultrasound-guided local treatments. Clin Orthop Relat Res. 2015;473(1):119-125. doi:10.1007/s11999-014-3812-6.
104. Brophy RH, Fillingham YA. AAOS clinical practice guideline summary: Management of osteoarthritis of the knee (Nonarthroplasty), third edition. J Am Acad Orthop Surg. 2022;30(9):e721-e729. doi:10.5435/JAAOS-D-21-01233.
105. Hunter CW, Deer TR, Jones MR, et al. Consensus guidelines on interventional therapies for knee pain (STEP Guidelines) from the American Society of Pain and Neuroscience. J Pain Res. 2022;15:2683-2745. doi:10.2147/JPR.S370469.
106. Lee DW, Pritzlaff S, Jung MJ, et al. Latest evidence-based application for radiofrequency neurotomy (LEARN): Best practice guidelines from the American Society of Pain and Neuroscience (ASPN). Journal of Pain Research. 2021;14:2807–2831. doi:10.2147/JPR.S325665.
107. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee [published correction appears in Arthritis Care Res (Hoboken). 2021 May;73(5):764. doi: 10.1002/acr.24615]. Arthritis Care Res (Hoboken). 2020;72(2):149-162. doi:10.1002/acr.24131.
108. Moseng T, Vliet Vlieland TPM, Battista S, et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update. Ann Rheum Dis. 2024;83(6):730-740. doi:10.1136/ard-2023-225041.
109. Das G, Surange P, Agarwal A, et al. Radiofrequency ablation in chronic pain syndromes: an evidence-and consensus-based Indian Society for the Study of Pain Guidelines, 2022. Indian Journal of Pain. 2022;36(Suppl 1):S2-S23.
110. Shane A, Bailey S. Radiofrequency ablation for chronic knee, hip, and shoulder pain: CADTH Health Technology Review. Canadian Journal of Health Technologies. 2023;3(10).
111. Thomson L, Aujla RS, Divall P, Bhatia M. Non-surgical treatments for Morton's neuroma: A systematic review. Foot Ankle Surg. 2020;26(7):736-743. doi:10.1016/j.fas.2019.09.009.
112. Matthews BG, Hurn SE, Harding MP, Henry RA, Ware RS. The effectiveness of non-surgical interventions for common plantar digital compressive neuropathy (Morton's neuroma): a systematic review and meta-analysis. J Foot Ankle Res. 2019;12(1):12. doi:10.1186/s13047-019-0320-7.
113. Hau MYT, Thomson L, Aujla R, Madhadevan D, Bhatia M. Medium-term results of corticosteroid injections for Morton's neuroma. Foot Ankle Int. 2021;42(4):464-468. doi:10.1177/1071100720966332.
114. Choi JY, Lee HI, Hong WH, Suh JS, Hur JW. Corticosteroid injection for Morton's interdigital neuroma: A systematic review. Clin Orthop Surg. 2021;13(2):266-277. doi:10.4055/cios20256.
115. Millán-Silva MO, Munuera-Martínez PV, Távara-Vidalón P. Infiltrative treatment of Morton's neuroma: A systematic review. Pain Manag Nurs. 2024;25(6):628-637. doi:10.1016/j.pmn.2024.06.005.
116. Orhurhu V, Huang L, Quispe RC, et al. Use of radiofrequency ablation for the management of headache: a systematic review. Pain Physician. 2021;24(7):E973-E987.
117. Mustafa MS, Bin Amin S, Kumar A, et al. Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis. BMC Neurol. 2024;24(1):330. doi:10.1186/s12883-024-03834-6.
118. Evans AG, Joseph KS, Samouil MM, et al. Nerve blocks for occipital headaches: A systematic review and meta-analysis. J Anaesthesiol Clin Pharmacol. 2023;39(2):170-180. doi:10.4103/joacp.JOACP_62_21.
119. Velásquez-Rimachi V, Chachaima-Mar J, Cárdenas-Baltazar EC, et al. Greater occipital nerve block for chronic migraine patients: A meta-analysis. Acta Neurol Scand. 2022;146(2):101-114. doi:10.1111/ane.13634.
120. Ornello R, Lambru G, Caponnetto V, et al. Efficacy and safety of greater occipital nerve block for the treatment of cluster headache: a systematic review and meta-analysis. Expert Rev Neurother. 2020;20(11):1157-1167. doi:10.1080/14737175.2020.1809379.
121. Shauly O, Gould DJ, Sahai-Srivastava S, Patel KM. Greater occipital nerve block for the treatment of chronic migraine headaches: A systematic review and meta-analysis. Plast Reconstr Surg. 2019;144(4):943-952. doi:10.1097/PRS.0000000000006059.
122. Zhang H, Yang X, Lin Y, Chen L, Ye H. The efficacy of greater occipital nerve block for the treatment of migraine: A systematic review and meta-analysis. Clin Neurol Neurosurg. 2018;165:129-133. doi:10.1016/j.clineuro.2017.12.026.
123. Gordon A, Roe T, Villar-Martínez MD, Moreno-Ajona D, Goadsby PJ, Hoffmann J. Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review. J Neurol Neurosurg Psychiatry 2024;95(1):73-85. doi:10.1136/jnnp-2023-331066.
124. Oliveira KD, Dhondt N, Englesakis M, Goel A, Hoydonckx Y. Pulsed radiofrequency neuromodulation of the greater occipital nerve for the treatment of headache disorders in adults: A systematic review. Canadian Journal of Pain. 2024;8(1): doi:10.1080/24740527.2024.2355571.
125. Malekian N, Bastani PB, Oveisgharan S, Nabaei G, Abdi S. Preventive effect of greater occipital nerve block on patients with episodic migraine: A randomized double-blind placebo-controlled clinical trial. Cephalalgia. 2022;42(6):481-489. doi:10.1177/03331024211058182.
126. Chowdhury D, Datta D, Mundra A. Role of greater occipital nerve block in headache disorders: A narrative review. Neurol India. 2021;69(Suppl 1):S228-S256. doi:10.4103/0028-3886.315993.
127. Ertilav E, Aydın ON. Comparison of the efficacy of repeated greater occipital nerve block and pulsed radiofrequency therapy in chronic migraine patients: a randomized controlled study. J Oral Facial Pain Headache. 2024;38(3):100-107. doi:10.22514/jofph.2024.031.
128. Gul HL, Ozon AO, Karadas O, Koc G, Inan LE. The efficacy of greater occipital nerve blockade in chronic migraine: A placebo-controlled study. Acta Neurol Scand. 2017;136(2):138-144. doi:10.1111/ane.12716.
129. Inan L, Inan N, Karadaş Ö, et al. Greater occipital nerve blockade for the treatment of chronic migraine: A randomized, multicenter, double‐blind, and placebo‐controlled study. Acta Neurologica Scandinavica. 2015;132(4):270-277. doi:10.1111/ane.12393.
130. Cohen SP, Peterlin BL, Fulton L, et al. Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness. Pain. 2015;156(12):2585-2594. doi:10.1097/j.pain.0000000000000373.
131. Kissoon NR, O'Brien TG, Bendel MA, et al. Comparative effectiveness of landmark-guided greater occipital nerve (GON) block at the superior nuchal line versus ultrasound-guided GON block at the level of C2: A randomized clinical trial (RCT). Clin J Pain. 2022;38(4):271-278. doi:10.1097/AJP.0000000000001023.
132. Babaoğlu G, Dadali Ş, Sabuncu Ü, et al. Effectiveness of distal versus proximal greater occipital nerve pulsed radiofrequency in migraine management: a prospective randomized controlled trial. Turk J Med Sci. 2025;55(3):602-612. doi:10.55730/1300-0144.6007.
133. Barad M, Ailani J, Hakim SM, Kissoon NR, Schuster NM. Percutaneous interventional strategies for migraine prevention: A systematic review and practice guideline. Pain Med. 2022;23(1):164-188. doi:10.1093/pm/pnab236.
134. May A, Evers S, Goadsby PJ, et al. European Academy of Neurology guidelines on the treatment of cluster headache. Eur J Neurol. 2023;30(10):2955-2979. doi:10.1111/ene.15956.
135. Staudt MD, Hayek SM, Rosenow JM, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines for occipital nerve stimulation for the treatment of patients with medically refractory occipital neuralgia: update. Neurosurgery. 2023;93(3):493-495. doi:10.1227/neu.0000000000002578.
136. Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr SL. 2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2026;66(1):53-76. doi:10.1111/head.70016.
137. Puledda F, Sacco S, Diener H-C, et al. International Headache Society global practice recommendations for the acute pharmacological treatment of migraine. Cephalalgia. 2024;44(8):03331024241252666. doi:10.1177/03331024241252666.
138. Haq II, Banerjee AA, Arshad Z, Iqbal AM, Bhatia M. The management of tarsal tunnel syndrome: a scoping review. J Clin Orthop Trauma. 2024;54:102489. doi:10.1016/j.jcot.2024.102489.
139. Ritt MWJ, Koning H, van Dalen BV, Ter Meulen BC. Tibial nerve block as treatment of chronic foot pain. Anesth Pain Med. 2023;13(1):e131180. doi:10.5812/aapm-131180.
140. Atesok K, Pierce J, Small B, Perumal V, Cooper T, Park J. The course of tarsal tunnel syndrome after ultrasound-guided Injections. Orthopedic Reviews. 2022;14(3):35455.
141. Andiman SE, Maron JS, Dandolu V, et al. Impact of treatment of pudendal neuralgia on pain: a systematic review and meta-analysis. Int Urogynecol J. 2025;36(1):35-58. doi.org/10.1007/s00192-024-06004-x.
142. Labat JJ, Riant T, Robert R, Amarenco G, Lefaucheur J-P, Rigaud J. Diagnostic criteria for pudendal neuralgia by pudendal nerve entrapment (Nantes criteria). Neurourol Urodyn. 2008;27(4):306-310. doi.org/10.1002/nau.20505.
143. Labat JJ, Riant T, Lassaux A, et al. Adding corticosteroids to the pudendal nerve block for pudendal neuralgia: a randomised, double-blind, controlled trial. BJOG. 2017;124(2):251-260. doi:10.1111/1471-0528.14222.
144. Elsawy S, Fergani A, Herdan R, et al. Safety and efficacy of pulsed radiofrequency versus pulse dose mode radiofrequency targeting the pudendal nerve in patients with pudendal neuralgia: a prospective randomized controlled clinical trial. Minerva Anestesiol. 2025;91(5):413-421. doi:10.23736/S0375-9393.25.18678-1.
145. Fang H, Zhang J, Yang Y, Ye L, Wang X. Clinical effect and safety of pulsed radiofrequency treatment for pudendal neuralgia: a prospective, randomized controlled clinical trial. J Pain Res. 2018;11:2367-2374. doi:10.2147/JPR.S167866.
146. Masala S, Calabria E, Cuzzolino A, Raguso M, Morini M, Simonetti G. CT-guided percutaneous pulse-dose radiofrequency for pudendal neuralgia. Cardiovasc Intervent Radiol. 2014;37(2):476–481. doi:10.1007/s00270-013-0679-y.
147. Levin D, Van Florcke D, Schmitt M, et al. Fluoroscopy-guided transgluteal pudendal nerve block for pudendal neuralgia: a retrospective case series. J Clin Med. 2024;13(9):2636. doi:10.3390/jcm13092636.
148. Basol G, Kale A, Gurbuz H, Gundogdu EC, Baydilli KN, Usta T. Transvaginal pudendal nerve blocks in patients with pudendal neuralgia: 2-year follow-up results. Arch Gynecol Obstet. 2022;306(4):1107-1116. doi:10.1007/s00404-022-06621-1.
149. Wang C-L, Song T. The clinical efficacy of high-voltage long-duration pulsed radiofrequency treatment in pudendal neuralgia: a retrospective study. Neuromodulation: Technology at the Neural Interface. 2022;25(8):1372-1377. doi:10.1111/ner.13401.
150. Vidaeff AC. Pudendal and paracervical block. Updated 4/15/25. Accessed 7/20/26.
151. Engeler D, Baranowski AP, Berghmans B, et al. EAU guidelines on chronic pelvic pain. Accessed 7/20/26.
152. Batten TJ, Evans JP, Burden EG, Mak WK, White W, Smith CD. Suprascapular nerve blockage for painful shoulder pathology - a systematic review and meta-analysis of treatment techniques. Ann R Coll Surg Engl. 2023;105(7):589-598. doi:10.1308/rcsann.2022.0026.
153. Harley JD, Austin CN, Harrison AK, Saltzman BM, Rao AJ. Intra-articular corticosteroid injection vs. suprascapular nerve block for adhesive capsulitis: a systematic review and meta-analysis of level I randomized controlled trials. J Shoulder Elbow Surg. 2026;35(2):e402-e415. doi:10.1016/j.jse.2025.05.037.
154. Shanahan EM, Ahern M, Smith M, Wetherall M, Bresnihan B, FitzGerald O. Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain. Annals of the Rheumatic Diseases. 2003;62(5):400-406. doi:10.1136/ard.62.5.400.
155. Scattergood SD, Hassan A, Williams M. Does a suprascapular nerve block reduce chronic shoulder pain at 3 months compared to standard non-operative care? A systematic review. Eur J Orthop Surg Traumatol. 2025;35(1):162. doi:10.1007/s00590-025-04287-4.
156. Chang KV, Hung CY, Wu WT, Han DS, Yang RS, Lin CP. Comparison of the effectiveness of suprascapular nerve block with physical therapy, placebo, and intra-articular injection in management of chronic shoulder pain: A meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 2016;97(8):1366-1380. doi:10.1016/j.apmr.2015.11.009.
157. Bennett J, Patel N, Nantha-Kumar N, Phillips V, Nayar SK, Kang N. Assessing the effectiveness of suprascapular nerve block in the treatment of frozen shoulder: a systematic review and meta-analysis of randomized controlled trials. Bone Joint J. 2025;107-B(1):19-26. doi:10.1302/0301-620X.107B1.BJJ-2024-0644.R1.
158. Hou Y, Wang Y, Sun X, Lou Y, Yu Y, Zhang T. Effectiveness of suprascapular nerve block in the treatment of hemiplegic shoulder pain: a systematic review and meta-analysis. Front Neurol. 2021;12:723664. doi:10.3389/fneur.2021.723664.
159. Smith N, Liew Z, Johnson S, Ellard DR, Underwood M, Kearney R. A systematic review of the methods and drugs used for performing suprascapular nerve block injections for the non-surgical management of chronic shoulder pain. Br J Pain. 2021;15(4):460-473. doi:10.1177/2049463721992091.
160. Saglam G, Alisar DÇ. A comparison of the effectiveness of ultrasound-guided versus landmark-guided suprascapular nerve block in chronic shoulder pain: A prospective randomized study. Pain Physician. 2020;23(6):581-588.
161. Kamal K, Dahiya N, Singh R, Saini S, Taxak S, Kapoor S. Comparative study of anatomical landmark-guided versus ultrasound-guided suprascapular nerve block in chronic shoulder pain. Saudi J Anaesth. 2018;12(1):22-27. doi:10.4103/sja.SJA_123_17.
162. Ahmed SA, Ahmed MB. Ultrasound guided radiofrequency ablation of the suprascapular nerve versus injection block technique: A comparative study in patients with chronic shoulder pain. Med J Cairo Univ. 2019;87(6):3859-64.
163. Adey-Wakeling Z, Crotty M, Shanahan EM. Suprascapular nerve block for shoulder pain in the first year after stroke: a randomized controlled trial. Stroke. 2013;44(11):3136-3141. doi:10.1161/STROKEAHA.113.002471.
164. Annison DR, Smith N, Salt E, Noblet T, Rangan A, McDaid C. Physical harms associated with suprascapular nerve block interventions in the non-surgical management of acute and chronic shoulder pain: A systematic review. Shoulder & Elbow. 2024;17(3):236-253. doi:10.1177/17585732241255679.
165. Benzon HT, Elmofty D, Shankar H, et al. Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, and the International Pain and Spine Intervention Society ,and the North American Spine Society. Reg Anesth Pain Med. 2025;rapm-2024-105593. doi:10.1136/rapm-2024-105593.
166. Sconfienza LM, Adriaensen M, Albano D, et al. Clinical indications for image guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-part III, nerves of the upper limb. Eur Radiol. 2020;30(3):1498-1506. doi:10.1007/s00330-019-06479-z.
167. Texakalidis P, Xenos D, Karras CL, Rosenow JM. Percutaneous surgical approaches in multiple sclerosis-related trigeminal neuralgia: A systematic review and meta-analysis. World Neurosurg. 2021;146:342-350.e1. doi:10.1016/j.wneu.2020.11.006.
168. Kanpolat Y, Savas A, Bekar A, Berk C. Percutaneous controlled radiofrequency trigeminal rhizotomy for the treatment of idiopathic trigeminal neuralgia: 25-year experience with 1,600 patients. Neurosurgery. 2001;48(3):524-34. doi:10.1097/00006123-200103000-00013.
169. Moore D, Chong MS, Shetty A, Zakrzewska JM. A systematic review of rescue analgesic strategies in acute exacerbations of primary trigeminal neuralgia. Br J Anaesth. 2019;123(2):e385-e396. doi:10.1016/j.bja.2019.05.026.
170. Baykal M, Kaplan M. Effects of oral carbamazepine with 2% lidocaine on maxillary and mandibular nerve blocks in trigeminal neuralgia. Duzce Med J. 2010;12(3):19-23.
171. Balta S, Köknel Talu G. Clinical effectiveness of peripheral nerve blocks with lidocaine and corticosteroid in patients with trigeminal neuralgia. Agri. 2021;33(4):237-242. doi:10.14744/agri.2021.26032.
172. Elsheikh NA, Amr YM. Calcitonin as an additive to local anesthetic and steroid injection using a modified coronoid approach in trigeminal neuralgia. Pain Physician. 2016;19(7):457-464.
173. McMillan R, Zakrzewska J, Bahra A, et al. Guidelines for the management of trigeminal neuralgia. Royal College of Surgeons of England. 2021. Accessed 7/20/26.
174. Bendtsen L, Zakrzewska JM, Abbott J, et al. European Academy of Neurology guideline on trigeminal neuralgia. Eur J Neurol. 2019;26(6):831-849. doi:10.1111/ene.13950.
175. Mansano AM, Frederico TN, Valentin REB, Carmona MJC, Ashmawi HA. Percutaneous radiofrequency ablation for trigeminal neuralgia management: A randomized, double-blinded, sham-controlled clinical trial. Pain Med. 2023;24(3):234-243. doi:10.1093/pm/pnac132.
176. Shilash OB, Alqahtani L, Alkhaibary A, Khairy S, Alkhani A, Aloraidi A. Trigeminal neuralgia management in patients with multiple sclerosis: A systematic review of approaches and outcomes. J Clin Neurosci. 2025;136:111220. doi:10.1016/j.jocn.2025.111220.
177. Li Y, Yang L, Ni J, Dou Z. Microvascular decompression and radiofrequency for the treatment of trigeminal neuralgia: a meta-analysis. J Pain Res. 2019;12:1937-1945. doi:10.2147/JPR.S203141.
178. Abd-Elsayed A, Lee S, Jackson M. Radiofrequency ablation for treating resistant intercostal neuralgia. Ochsner J. 2018;18(1):91-93.
179. Hacıbeyoğlu G, Arıcan Ş, Ulukaya SO, Yılmaz R, Reisli R, Tuncer Uzun S. Evaluation of the efficacy of erector spinae plane block and intercostal nerve block in the postherpetic neuralgia. Agri. 2020;32(4):208-218. doi:10.14744/agri.2020.87523.
180. Eker HE, Cok OY, Aribogan A, Arslan G. Management of neuropathic pain with methylprednisolone at the site of nerve injury. Pain Medicine. 2012;13(3):443-451.
181. Li W, Tang L. Influence of greater occipital nerve block on the relief of acute migraine: A meta-analysis. Medicine (Baltimore). 2024;103(42):e39955. doi:10.1097/MD.0000000000039955.
182. Ashkenazi A, Blumenfeld A, Napchan U, et al. Peripheral nerve blocks and trigger point injections in headache management–a systematic review and suggestions for future research. Headache: The Journal of Head and Face Pain. 2010;50(6):943-952. doi:10.1111/j.1526-4610.2010.01675.x.
183. Ambrosini A, Vandenheede M, Rossi P, et al. Suboccipital injection with a mixture of rapid-and long-acting steroids in cluster headache: a double-blind placebo-controlled study. Pain. 2005;118(1-2):92-96. doi:10.1016/j.pain.2005.07.015.
184. Bushman ET, Blanchard CT, Cozzi GD, et al. Occipital nerve block compared with acetaminophen and caffeine for headache treatment in pregnancy: A randomized controlled trial. Obstet Gynecol. 2023;142(5):1179-1188. doi:10.1097/AOG.0000000000005386.
185. Cuadrado ML, Aledo-Serrano Á, Navarro P, et al. Short-term effects of greater occipital nerve blocks in chronic migraine: a double-blind, randomised, placebo-controlled clinical trial. Cephalalgia. 2017;37(9):864-872. doi:10.1177/0333102416655159.
186. Dadali S, Babaoglu G, Sabuncu U, Akcaboy EY. Comparison of the efficacy of ultrasound-guided repeated greater occipital nerve blocks and greater occipital nerve pulsed radiofrequency in migraine treatment. Pain Physician. 2025;28(4):337-346.
187. Caponnetto V, Ornello R, Frattale I, et al. Efficacy and safety of greater occipital nerve block for the treatment of cervicogenic headache: a systematic review. Expert Review of Neurotherapeutics. 2021;21(5), 591–597. doi:10.1080/14737175.2021.1903320.
188. Hokenek NM, Ozer D, Yılmaz E, et al. Comparison of greater occipital nerve and supra orbital nerve blocks methods in the treatment of acute migraine attack: a randomized double-blind controlled trial. Clinical Neurol Neurosurg. 2021;207:106821. doi:10.1016/j.clineuro.2021.106821.
189. Leroux E, Valade D, Taifas I, et al. Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10(10):891-897. doi:10.1016/S1474-4422(11)70186-7.
190. Tamayo de Leon CD, Gama-Reyes EG, Paredes Moreno FA, Galnares-Olalde JA. Adjunctive occipital nerve block for emergency treatment of acute migraine: A randomized, controlled trial. Cephalalgia. 2025;45(10):3331024251381764. doi:10.1177/03331024251381764.
191. Tanyel Saraçoğlu T, Bılır A, Güleç MS. Effectiveness of combining greater occipital nerve block and pulsed radiofrequency treatment in patients with chronic migraine: a double-blind, randomized controlled trial. Head Face Med. 2024;20(1):48. doi:10.1186/s13005-024-00449-7.
192. Krijnen EA, Schweitzer KJ, van Wijck AJM, Withagen MIJ. Pulsed radiofrequency of pudendal nerve for treatment in patients with pudendal neuralgia. A case series with long‐term follow‐up. Pain Pract. 2021;21(6):703-707. doi:10.1111/papr.12999.

References 182-192 were reviewed but not cited.

• Peripheral Nerve Blocks and Procedures for Chronic Pain
• Peripheral Nerve Blocks
• PNB
• Peripheral Nerve Injections
• PNI