Residency · Residency · Chronic Pain Management

Topical Analgesics: Lidocaine, Capsaicin, and Compounded Creams

Introduction

Topical analgesics offer the advantage of localized drug delivery with minimal systemic absorption, reducing the risk of systemic adverse effects and drug-drug interactions. They are particularly valuable in elderly patients, those with polypharmacy, and when pain generators are peripheral and well-localized. This lecture examines the evidence for topical lidocaine, capsaicin, topical NSAIDs, and the ongoing controversy surrounding compounded topical analgesics.

Topical Lidocaine

Mechanism of Action

Lidocaine blocks voltage-gated sodium channels (Nav1.7, Nav1.8) on peripheral nociceptors, reducing ectopic discharge from damaged or sensitized peripheral nerve fibers. The 5% lidocaine patch (Lidoderm) creates a local concentration gradient that desensitizes superficial nociceptors without producing anesthesia or numbness at labeled doses. An additional mechanism involves reduction of peripheral sensitization by decreasing spontaneous firing of A-delta and C fibers.

Evidence Base

The lidocaine 5% patch is FDA-approved only for postherpetic neuralgia (PHN), with an NNT of approximately 4.4 for at least 50% pain reduction. Off-label use is widespread for localized neuropathic pain, chronic low back pain, and osteoarthritis, though limited high-quality RCT evidence exists for conditions beyond PHN. The RELIEF trial (2020) found lidocaine patches non-inferior to pregabalin for localized neuropathic pain, supporting their role as first-line topical therapy.

Practical Prescribing

Up to three patches can be applied simultaneously to the area of maximum pain. The labeled regimen is 12 hours on, 12 hours off, though some practitioners prescribe continuous use — evidence for the safety of continuous application is limited but generally supportive. Systemic lidocaine absorption is minimal at labeled doses, approximately 3% of the applied dose. Patches can be cut to size for smaller areas. Common local reactions include mild erythema, edema, and irritation at the application site.

<image>Cross-sectional anatomical illustration of skin layers showing the mechanism of topical lidocaine patch action, depicting the drug penetrating from the patch through the stratum corneum and epidermis to reach nociceptive nerve endings in the dermis, with an inset showing sodium channel blockade at the molecular level and a diagram of the concentration gradient achieved at therapeutic depth versus systemic circulation</image>

Capsaicin

Mechanism of Action

Capsaicin is an agonist at the transient receptor potential vanilloid 1 (TRPV1) receptor. Initial application causes nociceptor activation, producing a burning sensation, followed by prolonged desensitization. With high-concentration application, this progresses to defunctionalization of nociceptive fibers — a reversible retraction of epidermal nerve fiber endings. Depletion of substance P from peripheral nerve terminals was previously thought to be the primary mechanism but is now considered secondary to the defunctionalization process.

Low-Concentration Capsaicin (0.025-0.075%)

Available over the counter as creams, gels, and roll-ons, low-concentration capsaicin requires 3-4 applications daily for 4-6 weeks before meaningful benefit is expected. The NNT for neuropathic pain is approximately 8-10 — modest efficacy at best. Adherence is poor because of the burning sensation and the demanding application schedule, and limited evidence supports clinically meaningful benefit over placebo.

High-Concentration Capsaicin 8% Patch (Qutenza)

The 8% capsaicin patch is FDA-approved for postherpetic neuralgia and EMA-approved for peripheral neuropathic pain more broadly. A single 60-minute application can provide pain relief lasting up to 12 weeks, with an NNT for PHN of approximately 7 for at least 30% pain reduction. The patch must be applied in a clinical setting by trained personnel. Pre-treatment with topical anesthetic (lidocaine 4% cream for 60 minutes) is recommended to manage the intense burning, erythema, and pain that occur during and immediately after application. Repeat applications can be given every 90 days as needed. A significant advantage is the complete avoidance of systemic effects and drug interactions.

<image>Step-by-step clinical procedure illustration for high-concentration capsaicin 8% patch application, showing: (1) marking the treatment area with a pen, (2) applying topical anesthetic cream, (3) removing anesthetic and cleaning skin, (4) applying the capsaicin patch with gloves, (5) timing the 60-minute application, and (6) removing and cleaning with provided cleansing gel, with an inset showing TRPV1 receptor activation and subsequent epidermal nerve fiber retraction at the histological level</image>

Topical NSAIDs

Available Formulations

Several formulations are available: diclofenac sodium 1% gel (Voltaren, now available OTC in the United States), diclofenac sodium 1.5% topical solution with DMSO (Pennsaid), diclofenac epolamine 1.3% patch (Flector), and ketoprofen gel (available in Europe but not in the US).

Evidence Base

The strongest evidence is for knee and hand osteoarthritis, with an NNT of approximately 6-10 for knee OA. Systemic plasma levels are approximately 5-15% of equivalent oral dosing. Cochrane reviews demonstrate efficacy equivalent to oral NSAIDs for superficial joint pain, but penetration to deep structures is limited, making topical NSAIDs less effective for hip OA and deep musculoskeletal pain. The gastrointestinal, cardiovascular, and renal risks are significantly reduced compared to oral NSAIDs.

Practical Considerations

Topical NSAIDs should be applied to intact skin only, avoiding wounds, mucous membranes, and eyes. Typical dosing for diclofenac gel is 4 g to the affected area four times daily (maximum 32 g per day for bilateral knees). Local skin reactions (dryness, erythema, pruritus) occur in approximately 5-10% of patients. These agents can be combined with oral analgesics as part of multimodal therapy. Cost has historically been a barrier, though OTC availability of Voltaren has improved access.

Compounded Topical Analgesics: The Controversy

Common Compounded Formulations

Compounded topical analgesics typically contain combinations of multiple agents — ketamine, gabapentin, baclofen, amitriptyline, lidocaine, diclofenac, cyclobenzaprine, and others — in bases designed to enhance transdermal penetration (PLO gel, Lipoderm, Versabase). They are marketed for neuropathic pain, musculoskeletal pain, CRPS, and various other conditions.

Evidence Assessment

The evidence does not support routine use. The landmark DoD/VA compounded topical pain cream study (2016-2019) found no significant difference between multi-agent compounded creams and placebo. Most individual ingredients lack evidence for transdermal absorption at clinically relevant concentrations. Gabapentin and amitriptyline have poor skin penetration and minimal evidence for analgesic effect when applied topically. Ketamine in topical form shows inconsistent evidence — some small studies suggest benefit for CRPS, but large trials are negative. The FDA does not regulate compounded medications for efficacy, safety, or quality in the same manner as commercially manufactured products.

Concerns

Compounded creams are often expensive ($200-800 per month) and may not be covered by insurance. There is no bioequivalence testing, meaning penetration and absorption vary between compounding pharmacies. Quality control issues include variability in potency, stability, and sterility. Ethical concerns have also been raised, as some providers have financial relationships with compounding pharmacies. Professional organizations including the AAPM have called for more rigorous evidence before routine prescribing.

<image>Comparative evidence summary diagram showing three columns for topical lidocaine, high-concentration capsaicin, and compounded topical creams, each with subsections displaying the strength of evidence (visualized as a bar from weak to strong), FDA regulatory status, NNT values where available, cost comparison, and a summary recommendation for clinical practice at the bottom of each column</image>

Clinical Pearls

Topical lidocaine patches are first-line for localized neuropathic pain, particularly PHN, offering an excellent safety profile with minimal systemic absorption. The high-concentration capsaicin 8% patch provides a unique mechanism-based approach with up to 12 weeks of relief from a single application, though it requires in-office administration. Topical NSAIDs are evidence-based for superficial joint osteoarthritis and should be considered before oral NSAIDs in elderly patients or those with gastrointestinal or cardiovascular risk factors. Compounded topical analgesics lack robust evidence for efficacy — the DoD/VA trial demonstrated no superiority over placebo, and routine prescribing is not supported by current evidence. Before recommending topical therapy, always assess whether the pain generator is superficial and localized, since deep structures and centrally mediated pain are unlikely to respond. Topical agents are ideal components of a multimodal strategy, particularly for reducing oral analgesic requirements.

References

1. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults — an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;5(5):CD008609.
2. Baron R, Allegri M, Correa-Illanes G, et al. The 5% lidocaine-medicated plaster: its inclusion in international treatment guidelines for treating localized neuropathic pain, and clinical evidence supporting its use. Pain Ther. 2016;5(2):149-169.
3. Brutcher RE, Kurihara C, Bicket MC, et al. Compounded topical pain creams to treat localized chronic pain: a randomized controlled trial. Ann Intern Med. 2019;170(5):309-318.
4. Derry S, Rice AS, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1(1):CD007393.

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