A review of nonsurgical neurolytic procedures for neuropathic pain
Journal article
Published on February 25, 2025
A review of nonsurgical neurolytic procedures for neuropathic pain

Contributors:

Gupta M, Abdallah RT, Abd-Elsayed A et al.

Name of journal:

Journal of Pain Research

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DOI:

10.2147/JPR.S491330

Topics:

DPN Lit review Narrative review Peripheral neuropathic pain Capsaicin 8% topical system
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This page provides a summary of Gupta M et al. J Pain Res. 2025;18:879–95. It is a simplified representation of the key points that was created by Averitas Pharma, and should not be considered a replacement for the full article or its abstract. Please refer to the original publication for further details and disclosures.

Summary

Understanding nonsurgical physical and chemical neurolytic procedures for treatment of neuropathic pain1

Learn more about the capsaicin 8% topical system mechanism of action.
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Background

Neuropathic pain can affect quality of life and may not respond to conventional treatments such as oral pharmacotherapies, leaving more than half of patients with insufficient pain reduction. As a result, symptoms often persist and become chronic.1

Physical and chemical nonsurgical neurolytic procedures can be used to alleviate neuropathic pain symptoms that are unresponsive to conventional treatments.1 These procedures involve the deliberate injury of peripheral nerves through freezing, heating, or application of chemicals, causing temporary degeneration of targeted nerve fibers and interrupting signal nerve transmission.1 Unlike damage to the central nervous system, peripheral nerves can regenerate following an injury.1

Aim

This narrative review provides a comprehensive overview of five nonsurgical neurolytic procedures commonly used to treat neuropathic pain and peripheral neuropathies.1

Physical neurolytic procedures

Cryoneurolysis and radiofrequency ablation (including thermal and pulsed methodologies) are physical neurolytic procedures that create well-circumscribed, spherical lesions to temporarily interrupt nerve conduction and relieve neuropathic pain.1

Cryoneurolysis

Cryoneurolysis utilizes extreme cold via an “ice ball” at the tip of a probe to interrupt nerve conduction and cause degeneration of myelin sheaths and axons.1 Nerve structures are preserved with cryoneurolysis, allowing nerve regeneration1

Radiofrequency ablation

Radiofrequency ablation uses heat generated via high-frequency alternating currents to create thermal neurodestructive lesions that interrupt nerve conduction1

Previous studies have shown that these neurolytic procedures can result in localized neuropathic pain relief which typically lasts 1 to 12 months, although repeat procedures are often needed.1,2–4

 

There is a potential risk of permanent nerve damage although the use of ultrasound or fluoroscopy guidance during the procedures have improved safety outcomes.1

Chemical neurolytic procedures

Two injectable chemoneurolytic agents, alcohol and phenol, and one topical chemoneurolytic agent, capsaicin 8% topical system, have been used to relieve neuropathic pain.1

Alcohol and phenol injection

Alcohol and phenol injections both function as nonselective chemoneurolytic agents.1 Once injected, both agents trigger a cascade of cellular events, which leads to degeneration of nerve fibers.1,5

Pain relief from injections may last up to 1 year with alcohol,6 and up to 6 months with phenol.3,7 Ultrasound or fluoroscopy guidance is necessary for both injections.1

Alcohol and phenol, being nonselective agents, can damage off-target tissues and cause post-treatment neuritis.1 Chemical neurolysis with alcohol or phenol are typically considered therapies of last resort and are not FDA-approved for neuropathic pain.1,a

Capsaicin 8% topical system

Capsaicin 8% topical system is an FDA-approved chemoneurolytic topical treatment for neuropathic pain associated with diabetic peripheral neuropathy of the feet.1,a

The topical system uses high-concentration capsaicin as a selective agonist of transient receptor potential vanilloid 1 (TRPV1) receptors.1,8 TRPV1 receptors play a key role in pain sensation and are primarily expressed peripherally on nociceptive fibers.1

The effects of capsaicin on pain modulation are complex and driven by multiple mechanisms.1 First, activation and overstimulation of TRPV1 receptors desensitizes TRPV1-expressing fibers, which suspends pain signals to the brain.1,8 Second, high-concentration capsaicin triggers a chemical cascade that results in temporary, reversible chemoneurolysis of the TRPV1-expressing nerve fibers.1,8

Learn more about the capsaicin 8% topical system mechanism of action.

The capsaicin 8% topical system has the potential for disease modification via nerve regeneration and restoration of function of cutaneous nerve fibers.1,9 Data from a 12-week, randomized, controlled phase 3 clinical trial, STEP, demonstrated that a single 30-minute application of capsaicin 8% topical system provided sustained pain relief for up to 12 weeks in patients with painful diabetic peripheral neuropathy of the feet.1,10 In addition, results from a 52-week, open-label, randomized trial, PACE, provided evidence of long-term safety with up to 7 repeat applications of capsaicin 8% topical system.1,11

In clinical trials, most treatment-emergent adverse drug reactions (ADRs) reported with the capsaicin 8% topical system were application-site reactions.1 These included burning, pain, erythema, pruritus, papules, swelling, and dryness, and were generally transient, self-limiting, and typically mild or moderate in intensity. No drug-related ADRs led to permanent discontinuation, and there were no drug-related serious ADRs or deaths.1

Conclusions

These physical and chemical nonsurgical neurolytic procedures provide patients and physicians with alternative options for the management of neuropathic pain; however, consideration of the risks and benefits is essential.1

Limitations

In this review, prospective analyses evaluating the safety and efficacy of each type of neurolytic procedure were included where possible; however, data for some procedures were limited to case studies and anecdotal evidence.1 Additional limitations include utilization of a single database (PubMed), English-language restriction, and inherent bias associated with non-systematic methodology.1

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Footnotes

aInformation updated in June 2025.

ADR, adverse drug reaction; FDA, United States Food and Drug Administration; TRPV1, transient receptor potential vanilloid 1.

QZA-03-25-0013 | June 2025