Peripheral Nerve Blocks and Procedures for Chronic Pain

Social Security Act (Title XVIII) Standard References:

• Title XVIII of the Social Security Act, section 1862(a)(1)(A). This section allows coverage and payment for only those services that are considered to be medically reasonable and necessary.
• 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, section 1833(e). This section prohibits Medicare payment for any claim which lacks the necessary information to process the claim.
• Title XVIII of the Social Security Act, section 1862 (a)(7) excludes routine physical evaluations.

Internet Only Manual (IOM) Citations:

• CMS IOM Publication 100-04, Medicare Claims Processing Manual,
  • Chapter 12, Section 50 Payment for Anesthesia Services
  • Chapter 23, Section 20.9 National Correct Coding Initiative (NCCI)
  • CMS IOM Publication 100-08, Medicare Program Integrity Manual,
    • Chapter 13, Section 13.5.4 Reasonable and Necessary Provision in an LCD

Internet Only Manual (IOM) Citations:

• CMS IOM Publication 100-04, Medicare Claims Processing Manual,
  • Chapter 12, Section 50 Payment for Anesthesia Services
  • Chapter 23, Section 20.9 National Correct Coding Initiative (CCI)
  • CMS IOM Publication 100-08, Medicare Program Integrity Manual,
    • Chapter 13, Section 13.5.4 Reasonable and Necessary Provision in an LCD
• CMS IOM Publication 100-03 Medicare National Coverage Determinations (NCD) Manual- Chapter 1 Section:
  • 30.3 – Acupuncture
  • 150.6 -Vitamin B12 Injections to Strengthen Tendons, Ligaments, etc of the Foot
  • 150.7 - Prolotherapy, Joint Sclerotherapy, and Ligamentous Injections with Sclerosing Agents

A. Trigeminal neuralgia

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

1. Condition has been present at least 6 months⁵³ AND

2. Non-responsive to medical therapy (such as carbamazepine or oxcarbazepine, phenytoin, baclofen) or intolerance of medical therapy¹²⁴ AND

3. Patient is not a good surgical candidate or declines surgical intervention¹²⁴ AND

4. Patient has had ≥ 75% improvement after diagnostic trigeminal nerve block.

Frequency limitation: Limited to (2) Radiofrequency Treatments (RFTs) within a rolling 12 months^42,53

B. Median neuropathy at the wrist, also known as carpal tunnel syndrome (CTS)

1. Corticosteroid (with or without local anesthetic) block may be used for the treatment of CTS.¹⁵
2. Peripheral nerve blocks (PNB) with local anesthetics (LA) only for the treatment of CTS are not medically reasonable and necessary and therefore non-covered.
3. Peripheral nerve denervation for CTS is not reasonable and necessary and therefore non-covered.

Frequency: Maximum of 3 steroid injections for CTS may be administered per lifetime per side.^12,13,15,22

C. Morton’s Neuroma

1. Corticosteroid (with or without LA) block may be used for the treatment of Morton’s neuroma^137,138

Frequency: A maximum of 2 steroid injections for Morton’s neuroma may be administered per lifetime per side.^137-139,141

Limitations

1. A PNB involves the use of an anesthetic and/or corticosteroid 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, 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 these procedures 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 in the specific patient.

4. PNBs and procedures to treat complex regional pain syndrome, 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.

5. "Dry needling" of neuromas, peripheral nerves are not medically necessary and will be non-covered procedures.

6. It is not routinely necessary for multiple injections or denervation such as epidural steroid injections, facet procedures, trigger point injections (TPI) to be provided to a patient on the same day as peripheral nerve procedures. If performed, the medical necessity of each procedure must be clearly documented in the medical record.

It is not reasonable and necessary for therapeutic PNBs, peripheral nerve denervation from ablation (RFA)* or cryoneurolysis for the treatment of:

*Peripheral nerve ablation includes thermal RFA, cooled RFA, pulsed RFA, water-cooled RFA and other percutaneous strategies such as balloon compression, glycerol rhizotomy, and microvascular decompression.

1. Occipital nerve block and denervation
2. Stellate ganglion block
3. Trigeminal nerve block
4. Suprascapular nerve block
5. Thoracic nerve block
6. Thoracic nerve denervation
7. Genicular nerve blocks (GNB), cryoneurolysis or ablation
8. Pudendal nerve block
9. Digital nerve block
10. Posterior tibial nerve block at the tarsal tunnel
11. Ulnar nerve block
12. Denervation of the trigeminal nerve for any diagnosis other than TN
13. Any other peripheral nerves blocks or denervations not listed above

Exceptions:

1. Regional anesthetic block
2. Acute surgical pain
3. Pain related to malignancy refractory to medical management

Chronic pain is pain that is experienced most days or every day in the past 3 months.¹ It is the most common reason adults seek medical care.² Chronic pain is associated with decreased quality of life,^3,4 opioid misuse,⁵ increased anxiety and depression,⁶ and unmet mental health needs.⁷

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.⁸

Prevalence of neuropathic pain may be as high as 7 to 8%, accounting for 20 to 25% of individuals with chronic pain.⁹ 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.¹⁰

PNBs 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. PNBs generally involve the administration of LA with or without corticosteroids using various techniques. PNBs may also have a role in diagnosing and informing subsequent treatments, such as radiofrequency ablation or cryoneurolysis for chronic pain conditions.¹

Denervation procedures aim to destroy a nerve to disrupt its ability to transmit pain signals and can be performed with heat (thermal) or cooled radiofrequency ablation and effects can be long lasting, but nerve regeneration is common. Cyroneurolysis uses extreme cold to freeze and disrupt nerve function causing temporary nerve function loss. The purpose of this Local Coverage Determination (LCD) is to provide the scope of indications that are supported as reasonable and necessary for the usage of PNBs and peripheral nerve ablation procedures for chronic pain management in appropriate patients.

Literature Analysis

This summary of the evidence is formatted by type of intervention and outcome classification (efficacy/effectiveness, undesirable effects, patient experience, physical performance, and health care utilization). The findings of published evidence syntheses (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 [Appendix].

Carpal Tunnel Syndrome Nerve Blocks

Overall Conclusions

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 injection. 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 paresthesias 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 certainly 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.

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.¹² 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 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 (SMD -0.77, 95% 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 injection (SMD -0.62, 95% CI -0.87 to -0.38; 7 RCTs, 499 participants; moderate-certainty evidence).

The durability 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.¹³ 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.¹⁴ Eight studies were included in the comparison of splinting with corticosteroid injections. Moderate-certainty evidence (downgraded once for risk of bias) 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 favored corticosteroid injection, the 95% confidence intervals (Cis) excluded clinically meaningful benefit for injection. 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 risk of bias 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 risk of bias) 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 risk of bias, 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 risk of bias) indicates that corticosteroid injection probably results in a higher rate of remission from nocturnal paresthesias 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).¹⁵ 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 Boston Carpal Tunnel Questionnaire (BCTQ). Hand function or pain probably do 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.

Undesirable Effects

Ashworth, et al. systematically reviewed the clinical evidence describing undesirable effects of corticosteroid injections compared to placebo.¹² 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.¹⁶ A systematic review concluded there is uncertainty about the risk of adverse effects between surgery and corticosteroid injections (very low-certainty evidence).¹⁵ 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).¹⁴ The certainty of evidence was downgraded to very low (once for risk of bias, once for imprecision, and once for inconsistency).

Patient Experience

Ashworth, et al. a systematic review measured HRQoL at up to 3 months of follow-up using the Short-Form 6 Dimensions questionnaire (scale from 0.29 to 1.0; higher is better).¹² Localized corticosteroid injection compared to placebo probably improved slightly (mean difference (MD) 0.07, 95% CI 0.02 to 0.12;1 RCT, 111 participants; moderate-certainty evidence). Lusa, et al. performed a systematic review in accordance with the Cochrane methodology.¹⁵ They found no data to estimate the difference in health-related quality of life [HRQoL] (very low-certainty evidence). Atroshi, et al. found that at 10 weeks both methylprednisolone groups had greater improvement than the placebo group in HRQoL measures (SF-36 bodily pain, and SF-6D scores) and higher treatment satisfaction (P < 0.025).¹⁷ At 24 weeks and 1 year, there were no differences between methylprednisolone and placebo in these outcomes (P > 0.100). No differences were found between the 80- and 40-mg methylprednisolone groups in any patient experience end point (P > 0.100). So, et al. reported the median satisfaction score (0 to 5, higher is better) for participants with CTS receiving local steroid injection or splinting.¹⁸ Median satisfaction was 3 in the splinting group and 5 in the corticosteroid injection group. HRQoL was reported in a systematic review that compared local corticosteroid injection to splinting.¹⁴ For short-term follow-up, the certainty of evidence was rated as low (downgraded once for risk of bias and once for imprecision as the 95% CIs overlapped with the MCID value of 0.074 points). The SMD was -0.25 (95% CI -0.77 to 0.27, 2 studies, 270 participants, I² = 57%) favoring corticosteroid. This translates to 0.05 points worse in EQ-5D-5L (95% CI 0.15 worse to 0.05 better, MCID 0.074 points). At the long term, moderate-certainty evidence (downgraded once due to risk of bias) indicates that splinting probably does not improve HRQoL compared with corticosteroid injection. The mean EQ-5D-5L score was 0.82 in the corticosteroid group and 0.01 points better (95% CI 0.04 worse to 0.05 better, 1 study, 234 participants) for those prescribed a splint.

Health Care Utilization

Ashworth, et al. performed a systematic review that assessed the requirements for surgery in patients receiving localized corticosteroid injections or placebo.¹² 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 RCT¹⁷ 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.¹³ 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 a RCT¹⁶ reported outcomes at 12 and 24 months including the number of patients referred for and undergoing CTS surgery, and healthcare utilization.¹⁹ 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].²⁰

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).²¹

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.²² 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.

Occipital Nerve Blocks (see Tables A and B)

Overall Conclusions

Patients receiving nerve blocks with or without glucocorticoid for occipital neuralgia, cervicogenic headache, chronic migraine 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.

Efficacy/Effectiveness

Systematic Reviews

Mustafa et al. conducted a SR/MA compromised of 8 studies (n=268) on the effectiveness of greater occipital nerve block in chronic migraine.²³ Using Cochrane risk of bias tool, they state low risk across all domains. However, there are risks of bias noted including blinding, randomization, selective reporting and some unknown risk with 2/8 without concerns. The duration of the studies ranged from 4 weeks to 3 months. Meta-analysis of 5/8 reported low heterogenicity and showed favorable results but did not reach statistical significance. The studies are downgraded based on imprecision (small samples size and short-term follow-up), and risk of bias 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.²⁴ Meta‑analyses of pain severity of nerve blocks compared with other treatment groups (i.e., neurolysis, pulsed radiofrequency, and BTX A) demonstrated a lack of improvement was seen 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, limited number of studies included, varied diagnoses (although all related to headache), injection techniques, medications, and modalities such as use of nerve stimulator-guided injections.²⁰

Velasquez-Rimachi, et al. performed a meta-analysis which included 3 RCTs (n=310) to evaluate greater occipital nerve block (GONB) LAs alone or with corticosteroids to prevent chronic migraine (CM).²⁵ At 2 month follow up, GONB achieved a reduction in headache intensity, but not frequency. Trial sequential analysis of the RCTs was inconclusive. Limitations include very low quality of the evidence due to substantial risk of bias and imprecision due to small sample size, short duration of follow up, variability in reported outcomes and measures and lacked inclusion of patient values.

Ornello, et al. conducted a meta-analysis of 5 studies to evaluate the evidence of efficacy and safety of GONB in cluster headaches (CH).²⁶ The studies reported a decrease in headache severity, intensity, and duration. Limitations included use of observational data, lack of robust studies included in analysis resulting in high heterogeneity, wide CIs, wide variation among study designs, short duration of follow up and unclear risk of bias.

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.²⁷ 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, use of Jadad scale for bias assessment, small number of included studies, limited sample size and duration of follow up, variations in randomization and blinding across studies.

Zhang, et al. conducted a SR/MA to investigate the efficacy of GONB with LA for migraine patients.²⁸ 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, 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.

Randomized Controlled Trials (RCTs)

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.²⁹ Patients with occipital neuralgia or cervicogenic headache may benefit from greater pain reduction at 4 weeks from USGONB as compared to LGONB. Limitations include subjects receiving BTX-A injections potentially causing indirectness. The study was underpowered for clinically meaningful results, imprecision resulting from 1 patient was lost to follow-up at week 4 analysis, small sample size, short-term follow-up, potential self-report bias, and results may not be generalizable.

Malkekian, et al. presented a single site double-blind placebo-controlled RCT to examine the efficacy of GONB in in 55 subjects (mean age 40.42 +12.23) suffering from episodic migraine without aura with steroid, lidocaine steroid + lidocaine or saline.³⁰ No significant difference between groups was reported. No injection was superior to the placebo regarding the duration and severity of the headaches. Limitations of this study included small sample size resulting in 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.

Undesirable Effects

Information about undesirable effects (i.e.; complication(s), adverse events, side effects) were reported in 4 systematic reviews,^24,25,27,28 3 RCTs,^{29,30 31} Two SRs reported serious adverse events: (1) reported in a placebo group with no details given²⁵ and (2) reported 6 days post GONB, benign intracranial hypertension. This participant was diagnosed with migraine and pseudotumor cerebri.²⁸ Aside from these, minor adverse effects were identified among studies. Reported adverse events included transient cervicalgia,³¹ worsening of headache following the injection, worsening of headache at 2 weeks, worsening and change in location of headache at 2 and 4 weeks, numbness and tingling in the occipital distribution, transient dizziness, lightheadedness, blurred vision, nausea with flushing, and injection site tenderness.²⁹ Triamcinolone was associated with adverse events in 3 subjects.³⁰ One SR reported adverse events in 50% (6/12) of the RCTs.²⁴ Another SR reported minor bleeding at the injection site.²⁵ Another SR reported vasovagal syncopal attack, transient dizziness, alopecia, immediate headache, benign intracranial hypertension, bloating, hypoesthesia, local pain at injection site, vertigo, nausea, back pain, cervical neck spasm, and transitory stinging sensation.²⁷ Adverse effects included injection site pain, abdominal distension, paresthesia, and fat redistribution.²⁸

Patient Experience

No measures of patient health care experience (satisfaction with treatment, health-related quality of life) were assessed.

Health Care Utilization

A SR reported GONB did result in a decrease in analgesic medication consumption.²⁸ A meta-analysis evaluated GONB LAs combined or with or without corticosteroids to prevent CM reported a reduction in headache intensity and frequency, but not duration at 1 and 2 months. The addition of corticosteroids yielded a minor difference of −1.1 days in favor of the addition of corticosteroids.²⁵

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. A RCT reported that USGONB achieved significant improvements in severe headache days.²⁹ Another RCT examined the efficacy of GONB in the prophylaxis of episodic migraines without aura and compared different injectable drug regimens in subjects with episodic migraines. The RCT reported groups who received LA alone and LA + triamcinolone showed a significant decrease in headache frequency compared to baseline (P=0.002, P=0.019, respectively).³⁰

A SR utilized injection treatments for headaches with pain or tenderness in the occipital scalp reported statistically significant reductions in headache frequency at 1-6 weeks compared with baseline and inactive control injections.²⁴ Another SR/MA evaluated GONB LAs combined with or without corticosteroids to prevent CM. The SR/MA concluded corticosteroids did not show a significant decrease in the frequency of headaches.²⁵ A SR assessed the efficacy of greater occipital nerve block in the treatment of CM headaches. They reported GONB resulted in a significant decrease in headache severity as compared to saline controls (p < 0.0121).²⁷ A SR investigated the efficacy of GONB with LA for migraine patients reported reduced pain intensity but not change in duration of headache.²⁸

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 GRADE methodology.³² The committee concluded:

• Greater occipital nerve blocks received a weak recommendation for use based on insufficient evidence for their use for CM prevention.
• For greater occipital nerve block, steroid(s) received a weak recommendation against its use vs the use of LA alone.

The European Academy of Neurology (EAN) 2023 guidelines for cluster headaches recommend occipital nerve block for cluster headaches.³³ This recommendation was based on consensus, and they acknowledge evidence is insufficient to issue evidence-based guidelines. The guidelines also utilize oral and intravenous (IV) steroids use for headache management.

Stellate Ganglion Nerve Blocks (SGB) (see Tables C and D)

Overall Conclusions

While there are some positive trends for SGB, there is a lack of high-quality data, defined patient selection and long-term outcome data for clinical application.

Complex Regional Pain Syndrome

Systematic Review

Tian, et al. conducted a SR/MA comprised of 12 RCTs (n=422) to compare the efficacy of sympathetic ganglion block (SGB) therapy for complex regional pain syndromes (CRPS) related with pain duration of at least 6 months.³⁴ They reported decrease in Visual Analog Scale (VAS) (4 studies), numeric rating scale (NRS) (3 studies), slight decrease in heart rate (1 study) and skin temperature (3 studies). Limitations included high heterogeneity, unclear allocation concealment in half included studies, limited number of studies included, and overall high risk of bias in included studies. Larger sample sizes with more robust RCTs are needed to confirm the efficacy of SGB in treatment of CRPS pain.

O’Connell, et al. conducted an updated review of the previously published work in 2005 on local anesthetic blockade (LASB) of the sympathetic chain to treat people with CRPS.³⁵ This review included 12 RCTs (N=461) which 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 quality of evidence to be low to very low. Due to the lack of high-quality evidence and paucity of literature, reviewers uphold 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 state that the current data does not suggest that LASB is effective for pain reduction in CRPS.

Craniofacial Postherpetic Neuralgia

US-Guided Stellate Blocks with Extracorporeal Shock Wave

Wang, et al. performed an RCT of 36 subjects with craniofacial postherpetic neuralgia (PNB) comparing ultrasound (US)-guided stellate ganglion block (SGB), extracorporeal shock wave therapy (ESWT) or both.³⁶ VAS and PDI decreased in all groups with the largest decrease in the combined treatments. Pain Disability Index (PDI) significantly decreased in all 3 groups as compared to baseline (P< 0.05). Authors conclude US-guided SGB with shock wave therapy is safe and effective and may significantly improve the pain in PHN patients. Limitations included being conducted at a single site, small sample size, limited duration of follow up, methodologic limitations: no description of randomization, allocation concealment, blinding approach, sample size calculation, and no control group resulting in high risk of bias, imprecision, and indirectness. May not be generalizable.

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 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 (Cohen d, 0.56 [SD, 0.09; 95%CI, 0.38-0.73]).³⁷ Six adverse events occurred with no serious adverse events reported. Authors concluded 2 SGB treatments 2 weeks apart reduce CAPS-5 TSSS over 8 weeks. Limitations included short duration of follow-up, limited sample size, lack of blinding for investigators and due to the nature of the treatment, unblinding of subjects may be present. Results may not be generalizable because of the strict inclusion criteria.

Undesirable Effects

Information about undesirable effects (i.e., complication(s), adverse events, side effects) was reported in a SR/MA comparing the efficacy of SGB therapy for CRPS-related pain. The most common adverse events in 3/12 (25%) of the studies were reports of dizziness and headache.³⁴

An updated review of the previously published work in 2005 on local anesthetic blockade (LASB) of the sympathetic chain to treat people with CRPS. Six of the 12 studies reported minor adverse events.³⁵

Subjects who received US-guided SGB with shock wave therapy experienced adverse events that included skin bruising and slight swelling in 3 subjects.³⁶

An RCT assessed the effect of ultrasound-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).³⁸

An RCT comparing SGB to placebo block reported 6 adverse events occurred with no serious adverse events being reported.³⁷

Patient Experience

US-guided SGB with shock wave therapy subjects reported a statistically significant decrease was observed in NPS when comparing post treatment to baseline of all 3 groups. In comparison between groups, the combined group (group C) achieved a more significant decrease.³⁶

Health Care Utilization

An RCT of 36 subjects with craniofacial PHN reported a statistically significant decrease in NPS when comparing post treatment to baseline of all 3 groups.³⁶

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.

An SR compared the efficacy of SGB therapy for CRPS with a reported decrease in VAS and NRS. The difference between groups was not statistically significant with the weighted mean difference (WMD) and the decreased NRS score was -1.14 mm.³⁴

An RCT of 36 subjects with craniofacial PHN reported a statistically significant decrease was observed in NPS when comparing post treatment to baseline of all 3 groups.³⁶

An RCT comprised of 102 subjects assessed the effect of ultrasound-guided stellate blocks with 3 volumes of 1% lidocaine (4, 6 and 8 mL) on the skin temperatures and pain of the hand, axilla, and face. No association was found between temperature increase and pain decrease (linear regression model; p = 0.114, 0.294, and 0.159, respectively).³⁸

An RCT to determine if paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) reported a greater reduction in mean change in CAPS-5 TSSS as compared to sham.³⁷

Trigeminal Neuralgia Nerve Blocks

Overall Conclusions

The evidence describing the efficacy/effectiveness of PNBs 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 PNBs for individuals with TN may result in no serious adverse events. There is low certainty evidence that suggests the addition of calcitonin to PNBs for the treatment of individuals with TN results in improved health outcomes. No evidence specific to PNBs was identified regarding measures of patient experience or health care utilization.

Efficacy/Effectiveness

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.³⁹ Of the 17 included studies, a single retrospective case series (N=13) included PNBs in conjunction with the oral administration of carbamazepine.⁴⁰ Patients reported complete relief of pain within 1-2 minutes following 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, small number of participants, and high risk of bias.

Randomized Controlled Trials (RCTs)

No RCTs were identified that compared the discrete effects of PNBs 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.⁴¹ 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 1600 patients (2138 procedures) with idiopathic TN with average follow-up time between 68.1 ± 66.4 months (range, 12–300 months).⁴² 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 (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 hypertension (HTN), fatigue, and nausea. Four studies failed to report the occurrence of adverse events, and 4 studies reported no adverse events appeared.³⁹

Elshiek, 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 calcitonin group had some degree of numbness and paresthesia on the side of the face that improved within 2 weeks.⁴³ 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.⁴¹

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%).⁴²

Patient Experience

No studies were identified that reported measures of HRQoL or satisfaction.

Health Care Utilization

No studies were identified that compared the discrete effects of PNBs to inert or active interventions on health care utilization outcomes.

Potential Effect Modifiers

Potential effect modifiers considered were patient characteristics and procedural techniques that meaningfully impacted the results for the critical outcomes of pain, function, health care utilization, and undesirable effects. Elsheikh, et al. conducted a single site double blind RCT of 33 participants (mean age ~46 years) that evaluated the effect of adding calcitonin to a PNB (LA and methylprednisolone) using a modified coronoid approach in management of TN pain.⁴³ A significantly longer duration of effective pain relief (VAS ≤ 3 ) was noticed in the calcitonin group (34.7 ± 14.2 weeks ) compared with the control group (16.2 ± 12.7 weeks), P < 0.0004, after the first block. The number of subsequent blocks over 12 months was also significantly less in the calcitonin group (P=0.0007). Additionally, the same RCT reported significantly less use of oral medications (e.g., carbamazepine, pregabalin, anticonvulsants) in the group that received calcitonin as a component of the PNB, P < 0.05. This study was judged to have a low risk of bias. Significant limitations included indirectness and imprecision.

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 TN management which outlines use of “infiltration/block anesthesia to trigger point” as an acute adjuvant medication when provided by dentally trained clinicians with 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.⁴⁴

The European Academy of Neurology (2019)
The European Academy of Neurology performed a systematic review of 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.”⁴⁵

Trigeminal Neuralgia Radiofrequency (See Tables E and F)

Overall Conclusions

While robust literature is lacking, the overall evidence for RFT of the trigeminal nerve for TN was consistently favorable for refractory TN.

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.⁴⁶ 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 risk of bias. Limitations include 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.^47-49 RFA showed a superior outcome of immediate pain relief compared to GR in 2 reviews of patients with non-multiple sclerosis (MS)-related TN,^47,49 while another SR/MA focused on MS-related TN found no differences in terms of immediate pain relief or pain recurrence.⁴⁸ Two reviews meta-analyzed data comparing RFA with BC.^48,49 Both reviews reported 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.⁴⁹

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.⁵⁰ Sozer, et al focused on patients with MS-related TN.⁵¹ 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 RF was associated with an increased incidence of postoperative anesthesia compared with GR and MVD.⁴⁹ Data pooled from 9 NRSI showed that compared with RFA, MVD had a lower risk of requiring a secondary procedure or facial numbness.⁵² In contrast, MVD was more likely to increase the risk of hypacusis (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.⁵⁰ The occurrence rates of numbness following RFA were 40% and 18.7% at 3- and 12-months, respectively.⁴⁶ 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.⁴⁶

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.⁵² Sozer, et al. reported the time to second or third procedures and time to relapse did not differ significantly between RFA, MVD, or gamma knife radiosurgery.⁵¹ 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%).⁴⁶

Potential Effect Modifiers

Abduhamid, et al. compared RFA of the Gasserian ganglion and peripheral branches of trigeminal nerve in terms of efficacy and rate of complications.⁵³ 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).⁵⁴ 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.

An 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 pulsed radiofrequency procedure (PRF).⁵⁵ 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 one patient, while no adverse events were reported in the PRF group.

Suprascapular Nerve Blocks (See Tables G and H)

Overall Conclusions

Low certainty evidence suggests that RFA compared to sham intervention may result in a clinically significant reduction in 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).

Efficacy/Effectiveness Outcomes

Systematic Reviews

Scattergood, et al. assessed the effectiveness of suprascapular nerve block (SSNB) compared to standard of non-operative care in shoulder pain reduction at 3 months in 5 RCTs (N= 343; range 40-180).⁵⁶ Authors state 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. For example, although the minimal clinically important difference (MCID) for the SPADI is 10 and the VAS estimates range between 1.4 and 3, the reviewers used an MCID of 2.2. Reviewers assessed risk of bias and had some concerns in 2 studies regarding deviation for intended intervention and measurement of outcome. Other limitations include short follow up periods, injectant variability, and variability in reporting.

Annison, et al. evaluated the physical harm associated with the SSNB in the non-surgical management of shoulder pain.⁵⁷ This systematic review included 5062 participants across 111 studies. A total of 168 individual episodes of harm were reported among 4142 participants (4%) receiving SSNB intervention. Local pain and bruising were the most frequently reported harm reported with a low rate of 50/ 4142 (1.2%), but some serious adverse events were reported. Limitations of this systematic review include variability in terminology, follow up and techniques utilized and lack of reporting across included studies.

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 intra-articular injections in patients with chronic shoulder pain.⁵⁸ The authors reported improvement in pain as compared to placebo and PT, but not to intra-articular injections. This report was limited by moderate to high heterogeneity, short duration of follow-up, moderate sample size and some concerns about risk of bias.

Suprascapular Ultrasound versus Landmark-Guided

An 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).⁵⁹ At 3 months postinjection 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 lack of control group, indirectness due to the single study setting, and the short-term assessment.

An RCT with 50 subjects experiencing shoulder pain received SSNB under ultrasonographic guidance with anatomical landmark‑guided (LMG) technique.⁶⁰ Both the groups showed statistically similar improvement of VAS, range of motion (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 risk of bias.

A small RCT compared ultrasound guided RFA of the suprascapular nerve to injection block technique in 20 subjects at a single site [Egypt].⁶¹ At 6 months no pain was reported using VAS score (n=3). This study had risks of bias due to uncertainty randomization process and allocation concealment. Limitations include lack of blinding and very small sample size.

Undesirable Effects

No information about undesirable effects (i.e., complication(s), adverse events, side effects) were reported.^58,62 A SR evaluated physical harm associated with SSNB and reported local pain, bruising, transient motor weakness, pre-syncope and vasovagal syncope, paranesthesia/anesthesia, nausea, pneumothorax, and peripheral nerve injury. No cases of local anesthetic systemic toxicity (LAST) or serious infection requiring treatment were reported. Single instances of harm reported included unrelated death, upper limb swelling, facial flushing, seizure, and chest pain. A total of 168 individual episodes of harm were reported among 4142 participants (4%) receiving SSNB intervention with local pain and bruising being the most frequently harm reported with a low rate of 50/ 4142 (1.2%).⁵⁷

Patient Experience

Measures of patient health care experience (e.g., satisfaction, quality of life) were captured in a single prospective, randomized study. Outcomes were measured over the short term (<3 months). Health Assessment Questionnaire (HAQ) were reported and showed significant improvement in 1 week and 1 month as compared to baseline in both groups. No significant differences were reported between LG-SSNB and US-guided SSNB groups at baseline, 1 week, 1 month, and 3 month follow up.⁵⁹

Health Care Utilization

A single prospective, randomized trial assessed the impact of SSNB by utilizing different techniques. In a trial that compared US-guided to landmark-guided approaches, there was no difference in injectant reported.⁵⁸ A SR assessed the effectiveness of SSNB compared to standard of non-operative care in shoulder pain reduction at 3 months follow up. Two studies assessed participants with adhesive capsulitis (AC), 1 study rotator cuff tear, 1 shoulder impingement (SIS) and 1 osteoarthritis (OA) or rheumatoid arthritis (RA). Four studies compared SSNB to a steroid injection and 1 compared to placebo, 3 studies used anatomical landmarks to perform the SSNB and 2 performed using US guidance.⁵⁶

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. A single prospective, randomized trial (N=72), Saglam, et al. compared the effectiveness of ultrasound-guided injection to the blind SSNB group where both groups achieved statistically significant improvements in pain scores at 3 months as compared to baseline.⁵⁹ 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 not any injection-related side effects reported in either group.

A systematic review comprised of 5 RCTs assessed the effectiveness of SSNB compared to standard of non-operative care in shoulder pain reduction at 3 months follow up. Two studies conducted by SSNB with LA and corticosteroid resulted in a significant reduction in pain at 3 months.⁵⁶

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 ins shoulder pain following SSNBs, but lacked a comparison to LA with and without corticosteroid.⁶³

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 suprascapular nerve block results in pain relief and improves range of motion in patients with chronic shoulder pain, without clear superiority compared to a palpation-guided procedure.⁶⁴ 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 pulsed radiofrequency ablation of the suprascapular nerve for adhesive capsulitis combined with physical therapy provides good clinical outcome at 12 weeks follow-up. Level of evidence: 2 Clinical trials demonstrate that the application of pulsed radiofrequency 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 follow-up. The combination of physical therapy and radiofrequency is reported as more effective when compared with physical therapy alone. Level of agreement: 88.9%” In statement no. 5 is states “Ultrasound-guided suprascapular nerve block 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 suprascapular nerve block compared with ultrasound-guided subacromial steroid injection. Level of agreement: 88.9%.”⁶⁴

Thoracic Nerve Blocks

Overall Conclusions

The certainty of evidence is very low, and it is uncertain if there is a benefit for thoracic nerve blocks for chronic pain.

All Outcomes

A single retrospective case-control study (N=39; mean age ~55 years) compared the observed effects of intercostal nerve blocks (INB) and erector spinae plane (ESP) blocks in the treatment of PHN.⁶⁵ 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 Radiofrequency Ablation

No studies were identified that met the inclusion criteria.

Ganglion Impar Blocks for Coccydynia and Chronic Perineal Pain (See Tables I and J)

Overall Conclusions

The certainty of evidence was judged to be very low due to a high risk of bias, imprecision, indirectness, and inconsistency. It is very uncertain whether ganglion impar blocks (GIB) have a benefit in the treatment of chronic coccydynia and perineal pain.

Efficacy/Effectiveness

The effectiveness of GIB was evaluated in 2 systematic reviews, 2 RCTs, and 3 NRSI [Table I]. All the primary studies took place at single facilities located outside the USA. Participants in these studies had varying etiologies for their pain (e.g., trauma and idiopathic origins), with pain duration extending beyond 3 months. Complaints were reportedly refractory to more conservative interventions. Pain was the primary outcome for every study [Table J]. Other efficacy outcomes included functional measures and failure rates. Authors in these studies disclosed no conflicts of interest, and there was no mention of industry funding.

GIB versus RFA

Two systematic reviews arrived at inconsistent findings. Andersen, et al., systematically reviewed 8 studies (1 RCT, 1 retrospective cohort, and 6 case series), finding RFA achieved clinically superior pre/post differences in pain intensity compared to GIB at a mean of 5.54 months following intervention.⁶⁶ In contrast, Choudhary, et al. reported data from 7 NRSI.⁶⁷ The between-group differences showed a clinically significant difference in the short term (3-4 weeks) favoring GIB. There was no significant difference in pain status between GIB and RFA in the long term (6 months). One systematic review reported the failure rate was similar 11% and 12% for GIB and RFA, respectively.

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 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 risk of bias (ROB) appraisal tool that employed a checklist approach with an unweighted scoring scheme.⁶⁶

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.⁶⁸ 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.

There were 2 NRSI that compared GIB with RFA for patients diagnosed with chronic coccydynia.^69,70 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.

GIB versus Coccygeal Nerve Block (CNB)

One RCT compared the efficacy of GIB and CNB in treating chronic coccydynia.⁷¹ 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.⁷² 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.⁶⁶ 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.^67,68,70-73 Overall, the reported complications were few, with no serious adverse events observed in any patient.

Patient Experience

Three studies provided data regarding patient satisfaction. An RCT that compared 2 GIB techniques found all patients in both groups had excellent satisfaction immediately after intervention.⁷³ Two studies that compared GIB and RFA found consistent patient satisfaction results favored RFA.^68,70

Health Care Utilization

No data was reported.

Potential Effect Modifiers

Effect modifiers considered were patient characteristics and procedural techniques that meaningfully impacted the magnitude of results for the critical outcomes of pain, function, treatment success, and undesirable effects. One RCT and 5 NRSI were identified that assessed the effects of different procedural techniques.^73-78

An RCT reported GIB by the transsacrococcygeal or the transcoccygeal approach resulted in no statistically or clinically significant differences for pain, disability, and side effects, expecting disability at 3-months (the transcoccygeal approach showed statistically better improvement, P = 0.04). A single retrospective observational study reported that GIB may be more effective in cancer-related pain than pain due to benign causes in patients with chronic coccygeal and perineal pain.⁷⁵ The distribution pattern of contrast did not significantly affect the success of GIB treatment in patients with coccygodynia.⁷⁶ Different coccygeal dynamic patterns (normal and immobile coccyges) did not appear to affect the treatment outcome in GIB.⁷⁷ A retrospective cohort found there was no significant difference in pain relief from GIB between individuals with either normal or immobile coccyx mobility.⁷⁸ The presence of permanent coccygeal subluxation and prolonged symptom duration (>24.5 months) were found to have significant negative effects on treatment success (OR 9.56, 95% CI 1.44 to 63.40, p=0.02; OR 137.00, 95% CI 19.59 to 958.03, p<0.001), respectively.⁷⁴

Digital Nerves

Overall Conclusions

The available literature on digital nerve blocks was primarily comprised of case reports and literature reviews which lack high-quality, robust studies necessary to establish efficacy and safety.

Efficacy/Effectiveness Outcomes

Randomized Control Trials (RCTs)

Elsaman et al. evaluated the effectiveness of digital nerve block (DNB) in 83 (mean age 38.8 years) subjects with RA, more specifically, bilateral proximal interphalangeal (PIP) arthritis.⁸² 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 control in the group.

Systematic Review & Meta-Analysis

Ito et al. evaluated the efficacy of traditional (TD), transthecal (TT), and single subcutaneous (SC) palmar digital nerve block.⁸³ 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 which revealed major risks were reported including selection bias, unclear protocol including inclusion/exclusion criteria and failure to report outcomes. This study was limited due to inclusion of poor-quality studies, variations in anesthetic and amount administered.

Undesirable Effects

Adverse events included pain, tingling, and injection site bleeding with no significant differences reported between groups.⁸²

In the systematic review, 2 studies evaluated undesirable effects. In the traditional digital nerve block 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 subcutaneous palmar group, there was 1 case of infection (1.5%), 2 sensory impairment (2.9%), and 3 reported pain (4.4%). Two individuals reported injection site pain at 24 hours in the transthecal digital nerve block group (2/28; 7.1%). In the combined transthecal digital nerve block plus single SC palmar digital nerve block group, 3 individuals reported injection site pain (1/30; 3.3%).⁸³

Patient Experience

Two studies included in the systematic review evaluated patient satisfaction which reported 81.48% of the patients preferred the SC route (P = 0.0014). Another study reported 33% selected the traditional (TD) route, 25% of the subjects selected the SC route, and 43% selected the transthecal (TT) route. Subjects reported 33%, 25% and 43% satisfaction in TD, SC, and TT, respectively.⁸³

Healthcare Utilization

Mean outcome measures in RA clinical trials using the European League Against Rheumatism; OMERACT, score at 2 weeks for the active treatment versus control was 2.31±1.66 and 3.19±1.63 (P<0.001), respectively. At 8 weeks the active versus control was 2.55±1.43 and 3.14±1.35 (P=0.001), respectively. VAS at 2 weeks for the active treatment versus control was 40.8±17.1 and 56.5±19.7 (P<0.001), respectively. At 8 weeks the active versus control was 42.9±17.8 and 55.9±18.9 (P<0.001), respectively. Overall, the active group reported significantly less pain, swelling, tenderness, and US scores compared to the control at 2 and 8 week follow up.⁸³

Potential Effect Modifiers

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.⁸²

The efficacy of 3 methods of blocks including TD, TT, and single SC palmar digital nerve block were evaluated. No significant differences among the 3 approaches were reported.⁸³

Pudendal Nerve Blocks

All Outcomes

The literature search did not identify any evidence syntheses, RCTs, or comparative observational studies that investigated the effects of pudendal nerve blocks (PuNB) in patients with chronic pain disorders. A single retrospective cases series provided preliminary single-arm data. Levin, et al. reported on a study involving 101 patients with pudendal neuralgia (mean age 43.6 years) who received fluoroscopy-guided transgluteal pudendal nerve blocks.⁷⁹ 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.

Potential Effect Modifiers

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).⁸⁰ 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.

Clinical Guidelines and Positions of National and Specialty Organizations

European Association of Urology guideline on chronic pelvic pain has concluded, “There is a weak evidence base for these [GIB, PuNB] interventions for chronic non-malignant pain.”⁸¹

Genicular Nerve Blocks (GNB) (See Tables K and L)

Overall Conclusions

The certainty of evidence for minimally invasive interventions (e.g., GNB) for knee osteoarthritis (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.

Efficacy/Effectiveness

Systematic Reviews

Two systematic reviews with meta-analyses were identified as representative of the body of evidence for GNB.^84,85 Both evidence syntheses were published in 2025 and were critically appraised as high-quality reviews, using the validated AMSTAR-2 tool.⁸⁶ The characteristics and findings of the included clinical trials are recorded in Tables K and L, respectively.

Almeida, et al. assessed the efficacy and safety of minimally invasive interventions targeting the genicular nerves in knee osteoarthritis (KOA).⁸⁴ This meta-analysis included 8 RCTs (N = 518) that compared GNB to placebo/sham, intra-articular injections, physical therapies, alcoholic neurolysis, and RFA. The results showed the following:

GNB versus Saline (Sham)

The evidence is very uncertain based on a single study suggesting small improvements in pain and function at 4 weeks (downgraded for ROB, imprecision, and inconsistency).

GNB versus Intra-articular Injection Therapies

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).

GNB versus Physical Therapies

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).

GNB versus Alcoholic Neurolysis

The evidence is very uncertain based on a single study suggesting no difference in pain or function at 4 weeks, and alcoholic neurolysis showing better outcomes at 24 weeks (downgraded for ROB, imprecision, and inconsistency).

GNB + Intra-articular Injection therapy versus Intra-articular Injection therapy

The evidence is very uncertain based on 1 single study suggesting a small reduction in pain favoring the GNB + intra-articular therapy (IA), with minimal improvement in function (downgraded for ROB, imprecision, and inconsistency).

GNB versus RFA

Very low certainty evidence suggests that RFA may lead to small to moderate improvements in pain and function up to 24 weeks based on a single trial (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 (RA, juvenile idiopathic arthritis, perioperative knee pain, OA).⁸⁵ 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 (IACSI, physical therapy, 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.^87,88 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)

Two RCTs were identified that evaluated efficacy/effectiveness outcomes and were not included in either systematic review.^89,90

GNB versus RFA

Ghai, et al. randomly allocated 32 participants to receive either a genicular nerve block using local anesthetic and steroid (GNB-LAS) or ultrasound-guided pulsed radiofrequency ablation (PRFA) of the genicular nerve.⁸⁹ 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 HTN and diabetes, connective tissue disorders, neurological or psychiatric disorders, patients receiving intra-articular knee injection with steroid or hyaluronic acid 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.⁹⁰ 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 (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 methodological 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,^84,88 9 RCTs,^89-97 and 2 non-comparative NRSI.^98,99 Overall, there were no significant safety concerns (e.g., bleeding, 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.

Patient Experience

Measures of patient health care experience (e.g., satisfaction, quality of life) were captured in a single systematic review and 7 RCTs. Outcomes were measured over the short term (<3 months) in 6 RCTs. One small trial assessed patient experience outcomes up to 12 months.

HRQoL results reported in non-comparative studies (pre/post analyses) were systematically summarized, with statistically significant improvement in the SF-36 (physical and mental health domains) described by patients.⁸⁸ In addition to the systematic review, 3 RCTs assessed HRQoL. A trial designed to assess different GNB landmark techniques found statistically but not clinically significant differences in pain and social isolation in the short term. There were no significant differences at any time point for the dimensions of emotional reaction, sleep, physical mobility, or energy in the Nottingham Health Profile (NHP).⁹⁵ There were statistically significant between-group differences in the NHP dimensions of pain at 3 months (P = 0.03) and social isolation at 1 month (P = 0.01); however, none of these differences met minimal clinically important difference thresholds (35 and 27 points, respectively).¹⁰⁰ An RCT that enrolled 40 participants evenly allocated to receive intra-articular corticosteroid injection with or without GNB measured HRQoL using the NHP.⁸⁶ The between-group difference at 4 weeks was not statistically significant (P=0.372). During the 12^th week follow-up, there was a statistically significant difference in favor of the IACS + GNB group (P=0.001); however, the absolute difference of 3.26 points out of a possible 100 was unlikely to have been clinically meaningful. HRQoL was assessed using the SF-12 survey in an RCT that aimed to measure classical versus revised GNB landmark techniques.⁹⁷ There was no significant effect of group allocation on changes in SF-12 physical (P = .241) and mental scores (P = .098). Investigators reported no statistically significant differences between GNB and RFA in HRQoL measures at any follow-up assessment up to 12 months.⁹²

Patient satisfaction with treatment was assessed using the global perceived effect scale (GPES) in 3 RCTs. One study found statistically significant differences favoring GNB versus placebo injections at all time points.⁹¹ A trial (N=48) that compared anesthetic GNB with and without a corticosteroid showed at 4 weeks after the procedure patient satisfaction was better in the anesthetic plus corticosteroid group (global perceived effect, 4.7 ± 0.7) compared with the lidocaine alone group (3.6 ± 0.6; P < 0.001).¹⁰² Another RCT that investigated the effect of classical versus revised GNB landmark techniques reported the GPE score was not significantly different between groups at 4 and 12 weeks.⁹⁷

To summarize, differences between groups for HRQoL outcomes were not found to be clinically significant for any study at any time point. GPES scores favored GNB compared to placebo, and anesthetic GNB with adjunctive corticosteroid versus no corticosteroid, while different landmark techniques did not affect patient satisfaction.

Health Care Utilization

Two RCTs assessed the impact of GNB using different administration approaches on medication use. In a trial that compared classical versus revised GNB landmark techniques, there was no significant difference in medication use as assessed by the Quantitative Analgesic Questionnaire.⁹⁷ In a second RCT, there was no difference in the Medication Quantification Scale between groups receiving anesthetic GNB versus anesthetic GNB plus a corticosteroid during the 8-week follow-up period.¹⁰² Additionally, a small RCT reported on medication usage for comparative groups receiving either GNB or traditional RFA.⁹² The results showed reductions in oral opioid medication use were similar in both groups at 6 and 12 months (RFA: 57%, 71%; GNB: 44%, 67%, respectively).

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. Three RCTs and a single NRSI were identified that assessed the effects of different procedural techniques. In RCT (N=23), Cankurtaran, et al. compared the effectiveness of ultrasound-guided versus blind GNB in the treatment of KOA.⁹⁵ There were not any statistically significant differences between-group measures of pain and function at any follow-up period. A retrospective cohort-designed study (N=40) concluded that GNB administration using ultrasound guidance and anatomic landmark-guided techniques are both effective for significantly reducing pain, stiffness, and functional limitations in patients suffering from chronic KOA.¹⁰³ Among the 2 techniques, ultrasound-guided GNB appears to be more effective. Nevertheless, GNB guided by anatomic landmarks continues to be a viable treatment modality, especially in healthcare settings with limited to no ultrasonic facilities. Kim, et al. randomly compared the efficacy of ultrasound- vs fluoroscopy-guided GNB.⁹⁶ Pain relief, functional improvement, and safety were similar between groups receiving ultrasound- and fluoroscopy-guided GNB. The authors concluded that either of the 2 imaging devices may be utilized during a GNB for chronic KOA pain relief. Considering radiation exposure, ultrasound guidance may be preferred to fluoroscopic guidance. One RCT investigated the effects of adding a corticosteroid to anesthetic GNB.¹⁰² The authors reported the addition of a corticosteroid during GNB for chronic knee pain could prolong the analgesic effect and improve the functional capacity over the short term. However, the clinical benefit of this addition was not significant when compared with the benefit from local anesthesia alone. Given the potential adverse effects of corticosteroids, the addition of these agents to local anesthetics might not be warranted during GNB for chronic knee OA. In summary, there were no significant effect modifiers reported in the identified evidence. Informed patient preferences are likely important regarding procedural pain, radiation exposure, and consideration of the risk/benefit of corticosteroids.

Genicular Radiofrequency Ablation

Overall Conclusions

The use of related minimally invasive interventions (e.g., RFA) for knee OA is currently not supported by high-quality evidence. There is low certainty that RFA targeting the genicular nerves for KOA results in a reduction in pain or improvement in function. Despite some short-term reductions in pain reported with RFA compared to sham and other comparators, the overall benefits were inconsistent and minimal. We also have great uncertainty about their effects in the long term, as the available evidence is limited. The evidence supporting functional improvements was similarly weak, with most comparisons showing little to no significant difference. The very low certainty ratings across all comparisons indicate substantial uncertainty about the true effectiveness of RFA.

One high-quality⁸⁴ and 2 critically low-quality^104,105 systematic reviews were included in the summary of evidence.

Systematic Reviews

Almeida, et al. systematically assessed the efficacy and safety of minimally invasive interventions targeting the genicular nerves in KOA.⁸⁴ This meta-analysis included 17 RCTs (N = 1,463) that compared RFA to usual care, placebo/sham, intra-articular injection therapies (corticosteroid, PRP, hyaluronic acid), physical therapies, alcoholic neurolysis, and GNB. The reviewers summarized the findings as follows:

RFA versus Sham

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 risk of bias, 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.

RFA versus GNB

Very low certainty evidence suggests that RFA may lead to small to moderate improvements in pain and function up to 24 weeks based on a single trial (downgraded for risk of bias, imprecision, and inconsistency).

RFA versus alcoholic neurolysis

Very low certainty evidence 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 risk of bias, imprecision, and inconsistency).

RFA versus IA therapy

Very low certainty evidence suggests that 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 risk of bias, imprecision and incon¬sistency).

RFA versus usual care

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 risk of bias, imprecision, and inconsistency).

RFA + IA therapy versus IA therapy alone

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 risk of bias, imprecision, and inconsistency).

RFA + Stretching versus stretching

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 risk of bias, imprecision, and inconsistency).

The reviewers concluded that the use of related minimally invasive interventions (e.g., RFA) for knee OA is currently not supported by high-quality evidence. Despite some short-term reductions in pain reported with RFA compared to sham and other comparators, the overall benefits were inconsistent and minimal. We also have great uncertainty about their effects in the long term, as the available evidence is limited. The evidence supporting functional improvements was similarly weak, with most comparisons showing little to no significant difference. The very low certainty ratings across all comparisons indicate substantial uncertainty about the true effectiveness of RFA. As a result, any observed effects may not translate into meaningful clinical benefits for patients, and the therapeutic use of RFA should be approached with caution until more robust evidence is available.

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 genicular nerve blocks in predicting treatment outcomes.¹⁰⁴ 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 intra-articular injections. 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 outcomes¹⁰⁶ 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 were 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 for 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.¹⁰⁵ 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 intra-articular steroid injection, the probability of success was 4.5 times higher for RFA (relative risk = 4.58 [95% confidence interval = 2.61–8.04]). When RFA was compared with HA injection, the probability of treatment success was 1.8 times higher (relative risk = 1.88, 95% confidence interval = 1.38–2.57). The group mean functional scores improved in participants receiving genicular RFA compared to intra-articular steroid and hyaluronic acid 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/effectiveness outcomes and was not included in either systematic review.⁸⁹ This trial compared RFA with GNB and was summarized in the previous section.

Undesirable Effects

Information about undesirable effects (complications, adverse events, side effects), including bleeding, localized swelling and pain, motor weakness, and sensory deficit, was assessed in all the included systematic reviews, RCTs, and observational subset studies except 1 publication.¹⁰⁷ Broadly, no serious or long-term complications were observed during or following RFA procedures. Across studies, minor undesirable side effects included treatment site pain and subcutaneous bruising. These were infrequent and reportedly resolved within 3-5 days. One RCT (N=70) reported the rate of transient paresthesia was significantly higher (P = 0.011) in the genicular neurolysis cohort (34.4%) compared to the RFA cohort (6.3%).¹⁰⁸ An increase in pain after treatment was seen in 6.3% of the patients in the genicular neurolysis group, and there was no corresponding increase in pain in the RFA group.

Patient Experience

Measures of patient health care experience (satisfaction with treatment, health-related quality of life) were captured in 9 unique studies. Outcomes were measured over the short-term (<3 months) and intermediate term in 7 studies. Five trials reported on long-term patient experience measures.

The results of HRQoL outcomes were reported in 2 studies. Shen, et al. reported the RFA + intra-articular injection group displayed statistically significant improvement compared to the injection-only group immediately following intervention and at the 3-month assessment (P <0.05).¹⁰⁹ Clinical significance, however, was not reported. Chen, et al. indicated participants’ responses to the EQ-5D-5L health-related quality of life questionnaire suggested that those in the RFA cohort had a significantly improved overall health status compared with those in the hyaluronic acid injection cohort for up to 6 months following treatment.¹¹⁰

Satisfaction with treatment outcome was measured using various global perceived effect (GPE) scales in 8 unique studies. Three publications involving the same original study population found significantly greater proportions of participants reported their condition as “improved” on the GPE questionnaire at all follow-up time points in the cooled RFA cohort compared with the hyaluronic acid intra-articular injection cohort.^110-112 In another series of 3 publications of a unique population, superior perceived global effects for RFA compared to intra-articular injections at 1, 3, and 6 months were reported.¹¹³ These effects persisted in the RFA group at 12, 18, and 24 months.^114,115 Patient-reported satisfaction was measured using a Likert scale, with participants who randomly received either RFA or intra-articular PRP injections.¹¹⁶ In the short and intermediate terms, there were no between-group differences. At long-term follow-up (12 months), the PRP group had a significantly lower satisfaction value than the RFA group (P <0.001). El-Hakeim, et al. also assessed patient satisfaction with treatment using a Likert scale. The findings showed significantly higher values in the RFA group compared to conventional pharmacotherapy in the 3rd and 6th months.¹¹⁷ Kwon, et al. found no observable differences in satisfaction with treatment outcomes in participants who received RFA or sham RFA in the short and intermediate terms.¹¹⁸ Another RCT assessed RFA with sham RFA, where both groups received local anesthetic and corticosteroid injections.¹¹⁹ Satisfaction with treatment did not significantly differ at 12 months (P = 0.56). An RCT used the GPE scale to measure patient satisfaction with treatment between patients who received RFA vs. GNB.¹²⁰ The RFA group reported significantly (P < 0.01) better experiences in the short and intermediate terms. Another RCT compared RFA to GNB, finding nearly double the of the RFA group reported they were ‘very much satisfied’ or ‘very satisfied’ with treatment than those in the GNB group at 6 and 12 months (RFA: 65% at 6 months, 43% at 12 mos. vs. GNB: 35% at 6 mos., 21% at 12 mos.).⁷⁷

Health Care Utilization

Six RCTs assessed the impact of RFA compared to sham or other interventions on medication usage (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 not able to discriminate whether the pharmaceuticals were targeting KOA or other co-morbid conditions.

Two RCTs evaluated medication use between groups assigned to RFA or sham RFA.^118,119 Kwon, et al. reported that no differences were observed in medication change between groups based on data obtained from the MQS a short and intermediate time points.¹¹⁸ Another trial assessed patient diaries, finding there also no between-group differences in analgesic consumption at any time point in the short, intermediate, and long terms.¹¹⁹

Two RCTs reported on the comparative effects of RFA and GNB on medication use.^92,120 Ma, et al. used data from 112 participant diaries to assess analgesic medication use >6 months post-knee arthroplasty.¹²⁰ 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).⁹²

In a study population that spanned 2 publications, only 8 participants in the RFA group and 7 in the hyaluronic acid intra-articular injection group were taking opioid medications at baseline.¹¹⁰ No significant changes were observed from baseline to the 6- and 12-month follow-ups in the RFA and hyaluronic acid joint injection groups.^110,111 Overall, only 12 subjects were taking opioids for 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 CRFA group, whereas the opposite effect was noted in the hyaluronic acid injection group.¹¹⁰ At 12 months, there were no statistically different changes from baseline in either group with non-opioid pain medications (p = 0.6539).¹¹¹

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.^113,114 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 that 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.^121,122 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).¹²¹ 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).¹²² 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.¹²¹ At long-term follow-up, there was a statistically significant difference in the mean absolute numerical rating scale favoring cooled RF versus conventional RFA (P = 0.02). Differences between functional outcomes were not statistically significant.¹²² 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.¹²³

Sanatana-Pineda, et al. compared continuous and pulsed genicular RFA.¹²⁴ 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-months 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).¹²⁵ 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.¹²⁶ A total of 58.6% of participants in the diagnostic block group and 64.0% 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 compare it to the classic single-needle approach in 50 participants diagnosed with chronic KOA that was refractory to conservative treatment.¹²⁷ 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.

Genicular Cryoneurolysis

Overall Conclusions

There is moderate certainty evidence that genicular cryoneurolysis, compared to sham, results in little to no difference in KOA-related pain intensity in the short- and intermediate-term. There is moderate certainty evidence that genicular cryoneurolysis likely provides a clinically superior reduction of pain-related activity interference and overall functional improvement compared to sham intervention in the short and intermediate terms. There is moderate certainty evidence that genicular cryoneurolysis compared to sham results in little to no difference in undesirable effects and quality of life measures in the short and intermediate terms. Further research could have an important impact, which may change the estimates of effect.

The literature search identified 1 systematic review, 2 RCTs, and 1 NRSI that met eligibility criteria. Since the evidence base was limited, the summaries of the 2 studies were appraised without discrimination by design or outcome type.

All Outcomes

Cryoneurolysis vs. Sham

Radnovich, et al. conducted a double-blind, sham-controlled, multicenter (USA) RCT to evaluate the efficacy and safety/tolerability of cryoneurolysis for reducing pain and symptoms in patients with mild-to-moderate KOA.¹²⁸ 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 visual analog scale (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 change from baseline to Day 30 (primary endpoint), Day 60, and Day 90 than the sham treatment group. The mean difference between groups in WOMAC pain subscale score at Day 30 was 7.12 (95% confidence interval [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.¹²⁹ Among patients who continued to have a benefit at Day 120 and Day 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 Days 30, 60, and 90. The range of results included clinically relevant between-group differences at these time points, as well as on Day 120.

The mean difference 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, Day 90, or Day 120. Among patients eligible for follow-up past Day 120, those in the cryoneurolysis treatment group had a statistically significant mean difference 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.¹⁰⁶ 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 PGIC responders at any follow-up assessment.

Most of the expected side effects were mild in severity and resolved within 30 days. The most reported expected side effects were bruising, numbness, redness, tenderness upon palpation, and swelling. A total of 84 adverse events (AEs) were deemed possibly or probably related to the device or procedure. The incidence and severity of device or procedure-related AEs were similar in the 2 treatment groups.

This study was judged to have a low risk of bias. The primary limitations were that patients began to more accurately guess their treatment group assignment based on their response to treatment over time. 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).¹³⁰ 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 genicular nerve block, were included in the study. Before ultrasound-guided cryoneurolysis, transcutaneous electrical nerve stimulation and anatomic landmarks were used for nerve identification. The infrapatellar branch of the saphenous nerve (IBSN) 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). No serious adverse effects were reported throughout the study in either group. Several minor adverse effects were observed that were expected and defined before the study started, including altered sensation, bruising, local pain, numbness, redness, swelling, tenderness on palpation, and tingling. 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 quality of life.

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.

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.¹³¹ The study compared and contrasted 6 non-operative treatment modalities for KOA: cryoneurolysis with deep or both deep and superficial genicular nerve block (CryoDeep/Both), cryoneurolysis with superficial nerve block only (Cryo-Superficial), IA hyaluronic acid (IA-HA) injections, 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 minimally clinically important difference (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, JR). 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 < .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 .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.

Certainty of Evidence

There is low-certainty evidence from a single NRSI that intra-articular triamcinolone extended-release injections achieve greater clinically relevant improvements in pain and functional outcomes compared to either superficial or deep genicular cryoneurolysis in the short and intermediate terms.

Clinical Guidelines and Positions of National and Specialty Organizations

The American Academy of Orthopedic Surgeons guideline for the Management of Osteoarthritis of the Knee (Non-Arthroplasty) classified RFA as “denervation therapy,” along with chemical ablation.¹³² The guideline states that “denervation therapy may reduce pain and improve function in patients with symptomatic osteoarthritis of the knee.” The strength of this recommendation is noted to be limited due to inconsistent evidence and bias. Future research in the area should utilize clinically relevant outcomes and controls for bias. The guideline did not specifically include GNB or cryoneurolysis as candidate interventions for KOA.

The American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee did not include genicular nerve blocks or cryoneurolysis as potential interventions for KOA.¹³³ The guideline stated genicular RFA is conditionally recommended for the treatment of KOA. Although studies demonstrated potential analgesic benefits with various ablation techniques, the available studies lacked a standardized technique and controls were not uniform. There was also a lack of evidence showing long-term safety data.

The American Society of Pain and Neuroscience (ASPN) issued consensus guidelines applying the U.S. Preventive Services Task Force (USPSTF) grading criteria on the use of interventional therapies for knee pain (STEP Guidelines).¹³⁴ The guideline did not include GNB or cryoneurolysis as treatment options for KOA. ASPN provided the following consensus points for genicular nerve ablation:

1. RFA of the SM [superomedial], SL [superolateral], and IM [inferomedial] genicular nerves are 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.
2. RFA of the SM, SL, and IM genicular nerves can significantly reduce knee pain and improve function in patients with knee OA and pain refractory to TKA; Level 1, Grade A, Consensus Strong.
3. Thermal or cooled RFA should be utilized when performing GNA; Level 1, Grade A, Consensus Strong.

The 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.¹³⁵ The OARSI guidelines did not include RFA as a candidate treatment for KOA.

The 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.¹³⁶

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

Morton’s Neuroma Nerve Blocks

Overall Conclusions

There is moderate certainty evidence that the addition of corticosteroids to LA injection blocks 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.

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.^137,138 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. 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 a RCT, Hau, at al. evaluated the 5-year results of local anesthetic blocks with or without corticosteroid injections for Morton’s neuroma.¹³⁹ 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 were pooled for the purpose of this study. Thirty-four out of the original 36 patients (mean age of 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 that 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 (numbness, swelling, pain, mild skin atrophy, depigmentation) at the injection site reportedly occurred in 0–27% of patients.¹⁴⁰ No study described any serious adverse effects, e.g., hyperglycemia, infection, or tendon rupture.^140,141

Patient Experience

A systematic review stated that binary outcome measures from 6 studies demonstrated successful satisfaction following corticosteroid + local anesthetic intervention (34%, 95% CI: 21 to 49%) at a mean of 8.4 months.¹³⁸ Hau, et al. reported that 88% percent of the patients, after a single corticosteroid injection, were still satisfied with their outcome at 5-years post-intervention.¹³⁹

Health Care Utilization

Two systematic reviews reported similar rates (30%, 33%) of eventual transition to surgery within 12 months after steroid injection.^137,141 Hau, et al. obtained survey results from 34 of 36 patients who five years earlier had received a single injection of local anesthetic with or without corticosteroid injection for Morton’s neuroma.¹³⁹ 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-years 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-years 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).¹⁴¹

Overall Conclusions

There is moderate certainty evidence that the addition of corticosteroids to local anesthetic injection blocks 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.

Peripheral Nerve Blocks (Multiple Nerves)

Eker, et al.¹⁴² conducted a single site randomized controlled trial (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 Numerical Rating Scale (NRS) that was unresponsive to prior pharmacotherapy including NSAIDs, paracetamol and/or opioids The intervention involved ultrasound-guided nerve blocks 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 blocks 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-block pain reduction (P < 0.0001), but this did not persist at the 3-month follow-up. The methylprednisolone group maintained stable pain scores (post-block: 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 blocks for heterogeneous nerve targets, and the inability to assess the discrete effects of specific peripheral nerve blocks. The certainty of evidence was rated as very low (serious study limitations, indirectness, and imprecision).

Contractor Advisory Meeting

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

• The subject matter experts (SMEs) were favorable to the use of PNBs and RFA for genicular nerves after failed conservative measures stating level I evidence. They acknowledge challenges in literature including short term follow-up, randomization issues, and variables in outcome measures, however indicated SR/MA supported overall improvements. They stated lack of societal support or guidelines. They explained there is lack of evidence to set a threshold for diagnostic blocks to predict response to RFA and that many perform RFA without diagnostic blocks. There is no evidence to state if RFA or cryoneurolysis is superior.
• The SMEs felt there was little role for intercostal blocks outside of anesthesia.
• The SMEs state ganglion repair blocks for coccydynia are rarely used and not well studied.
• They discussed limited evidence for use of prudential nerve block for chronic pelvic pain.
• The SMEs state there is evidence to support the use of corticosteroid injections for CTS for short term use. They state there is no evidence for acute (<6 weeks) or long-term use. They explain 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 prior to injections for occipital neuralgia but there is evidence to support use for refractory headache. They explain it is supported by 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 stellate ganglion block for spasticity, but not hot flashes, post-traumatic stress syndrome or Bell’s palsy. The SMEs advocate a role for blocks in refractory chronic pain when they have difficulty participating in PT/OT.
• The SMEs explained 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.

This evidentiary analysis supports the reasonable and necessary use of percutaneous interventions for certain health conditions. There is moderate certainty evidence that localized corticosteroid injections for CTS are likely to provide clinically meaningful benefits with a low risk of serious undesirable effects for up to 6 months. While robust literature is lacking, the overall evidence for RFT of the trigeminal nerve for TN was consistently favorable. In cases where the patient is refractory to medical management there are limited treatment options short of surgical interventions which also lack robust evidence. Given that the risk with RFT of the TN is consistently low, a limited coverage criteria is included to ensure access when the patient has few options for a debilitating condition. This aligns with societal recommendations. There is moderate certainty evidence that the addition of corticosteroids to LA injection blocks likely results in a clinically significant benefit on pain associated with Morton’s neuroma.

Minimally invasive interventions (e.g., GNB) for KOA are not supported by high-quality evidence and there is substantial uncertainty about the true effectiveness of GNB. The CAC meeting discussed Level I evidence in the means of RCT to support these procedures, however on analysis, these studies were uniformly downgraded due to methodological concerns. To ensure we captured the breadth of literature we included systematic reviews and RCTs that were not included in the systematic reviews to ensure the totality of the literature was included. The result is uncertain, very low- and low-quality evidence leaving the true effect of these interventions unclear. Societies acknowledge the lack of high-quality evidence resulting in mostly limited or conditional recommendations. No organizational guidelines were identified that issued recommendations for the management of KOA using diagnostic GNB with or without RFA. Overall, there was moderate certainty in the evidence against percutaneous genicular nerve interventions.

The evidence for the use of occipital nerve blocks for management of chronic headaches is very low and low certainty and therefore not reasonable and necessary. Societal support is limited and based on consensus due to lack of certainty in the evidence. A diagnostic block is covered if clinical uncertainty exists in the diagnosis which may potentially provide temporary relief while other interventions are explored.

The balance of review findings indicates that the use of related minimally invasive interventions (e.g., nerve blocks, RFA, and cryoneurolysis) for the treatment of chronic non-cancer pain is currently not supported by high-quality evidence. PNBs, RFA, and cryoneurolysis, when compared to current standard of care therapies did not demonstrate consistent sustained improvements in pain, function, patient experience measures, and medication usage by a clinically important margin. The very low certainty ratings across comparisons indicate substantial uncertainty about the true effectiveness of these minimally invasive interventions. As a result, any observed effects may not translate into meaningful benefits for patients. The LCD utilizes a threshold of at least moderate certainty evidence for coverage consideration. Therefore, it remains to be determined whether these minimally invasive interventions are effective options for the treatment of chronic non-cancer pain conditions. Consequently, this evidentiary review advises against the addition of most of these interventions to standard reasonable and necessary treatment for Medicare beneficiaries diagnosed with chronic non-cancer pain.

Common study limitations across this evidence base were small sample sizes, inadequate length of follow-up to assess either the durability of benefits or the development of harm, high ROB, imprecision, indirectness, and lack of demonstrated clinical significance for some outcome measures, even when there was demonstrated statistical significance. For some chronic pain disorders, there was no evidence that allowed for causal conclusions about effectiveness. Some studies demonstrated a substantial placebo effect in the control group (i.e., participants who received a placebo or sham showed improvement in outcomes from baseline to follow-up measures). The relevant clinical practice guidelines provided conditional or no recommendations for PNBs, RFA, and cryoneurolysis.

Appendix

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. 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 B. Occipital Nerve Block: Findings of Included Studies

Table C. 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 D. 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 E. 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 F. 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

Table G. 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 H. Suprascapular Nerve Block: Findings of Included Studies

Table I. Ganglion Impar Blocks: Characteristics of Studies

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

Table J. 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 K. Genicular Nerve Blocks: 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 L. Genicular Nerve Blocks: 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

Associated LCDs

L34635 Botulinum Toxins Type A and B
L39624 Amniotic and Placental Derived Product Injections and/or Applications for Musculoskeletal Indications, Non-Wound

N/A

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