Capsaicin for Peripheral Neuropathy

Capsaicin has a prescription-strength patch for nerve pain, which makes the evidence unusually concrete and unusually split by strength. A Cochrane review of eight trials (2488 people) found that a single 8% capsaicin patch left about 10% more people much or very much improved than a control patch, in postherpetic neuralgia, HIV neuropathy and diabetic neuropathy. The review judged the added benefit 'not large', and it is similar to other chronic-pain treatments.

The creams people can buy without a prescription are a different story. A second Cochrane review of six trials (389 people) found too few data to judge low-concentration cream (below 1%); the information it had suggested no meaningful effect beyond placebo cream, which made a meaningful use in practice unlikely. The older BMJ meta-analysis was kinder to 0.075% cream, reporting a number needed to treat of 5.7, but it called the overall efficacy 'moderate to poor'. We rate this as mixed with limited evidence.

Cochrane describes the sequence: after application, capsaicin causes enhanced sensitivity to noxious stimuli, followed by a period of reduced sensitivity and, after repeated applications, persistent desensitisation. The 8% patch was developed to deliver more capsaicin quickly, so that cutaneous pain fibres are 'defunctionalised' fast, and its benefit is expected to last about 12 weeks.

The effect described is on pain signalling at the treated skin; the sources we read do not say that it repairs nerve damage.

Desensitising nerve endings sounds neat, but blinding is hard to maintain when the active treatment burns. Most high-concentration trials used a 0.04% capsaicin 'active placebo' to help maintain blinding, which may also narrow the measured difference between groups. The low-concentration review also warned that blinding remains a potential problem.

Trials of cream used 0.075% capsaicin applied several times daily for at least six weeks. The high-concentration patch is a single application of 8% capsaicin (about 100 times conventional cream strength), applied under highly controlled conditions, often after local anaesthetic, because of the initial intense burning sensation. If the pain returns, another application might be made after about 12 weeks.

The over-the-counter cream label we reviewed contains 0.025% capsaicin, to be applied as a thin film 3 to 4 times daily by adults 18 and over, with hands washed afterward. That product is labelled for minor muscle and joint aches, not for neuropathy.

The Cochrane update included eight randomised double-blind studies (2488 people), only one at high risk of bias. Six used 0.04% capsaicin as an active placebo. In postherpetic neuralgia (four studies, 1272 people), a two-study analysis of 571 people found about 10% more reported being much or very much improved at 8 and 12 weeks with the patch than with the control patch (moderate quality evidence). In painful HIV neuropathy, one study reported 27% improved on the patch versus 10% on the control at 12 weeks.

Reductions in pain intensity of 30% or 50% also favoured the patch by about 10%, with NNTs of 10 to 12, but this was very low quality evidence. A single diabetic neuropathy study (369 people) showed a similar 10% gain, and a small study of 46 people with persistent pain after hernia repair showed no difference. Serious adverse events were similar for capsaicin (3.5%) and control (3.2%).

The low-concentration review found six studies (389 people) of 0.075% cream, all published before 1996. Only two reported at least 50% pain relief, so no pooled analysis was possible. Local skin reactions were common, with a number needed to harm of 2.5. The authors concluded there were insufficient data to draw conclusions about efficacy, and that the information available suggests low-concentration capsaicin is without meaningful effect beyond placebo creams. The 0.025% over-the-counter cream label we reviewed is for minor aches, and no neuropathy trial of it was found.

The 2004 BMJ meta-analysis of six trials (656 patients) was more favourable: relative benefit 1.4 (95% CI 1.2 to 1.7) and NNT 5.7 for 0.075% cream in neuropathic conditions, with about a third having local adverse events. The reviewers still called the efficacy 'moderate to poor', useful for a small number of patients who cannot use or do not respond to other treatments.

A systematic review of six trials in postherpetic neuralgia found the between-group difference in mean percentage change in pain score ranged from -31 to -4.3, and all five meta-analysed studies favoured capsaicin. The authors called it a promising option for specific patients. Side effects were consistently higher, but could not be quantified.

What is missing: the Cochrane review found only one diabetic neuropathy trial (369 people), so evidence there is thin; the sources we read give little long-term safety data on repeated patches; and none tested capsaicin capsules for nerve pain.

Local reactions are the main issue. Burning at the application site was common across trials; with repeated low-dose cream the number needed to harm was 2.5, and the reactions were usually tolerable and eased with time. About one third of patients in the BMJ meta-analysis had local adverse events. Systemic side effects were rare.

The 8% patch has its own warnings. Its FDA label says patients may have substantial pain and burning during and after application even with local anaesthetic, that blood pressure can rise during or shortly after treatment (averaging under 10 mm Hg, though some rises were larger and lasted about two hours), that people with unstable or poorly controlled hypertension or a recent cardiovascular or cerebrovascular event may be at increased risk, and that it must not be applied to the face, eyes, mouth, nose or scalp.

The cream label warns that the burning sensation can be severe, tells users not to apply to wounds or damaged skin, and not to use if allergic to capsicum or chili peppers. Keep treated skin away from infants: LactMed reports severe pain in an infant who ingested capsaicin from the mother's skin, and advises against applying capsaicin to the breast or other areas a nursing baby might touch.

Topical capsaicin is poorly absorbed into the bloodstream, and systemic adverse effects were rare in the reviews. No interactions with oral medicines were reported in the sources we read. The label does say not to apply heat to the treated area immediately before or after use and not to wrap the area tightly.