Topical Capsaicin

A Review of its Pharmacological Properties and Therapeutic Potential in Post-Herpetic Neuralgia, Diabetic Neuropathy and Osteoarthritis



Capsaicin, the active principle of hot chilli pepper, is thought to selectively stimulate unmyelinated C fibre afferent neurons and cause the release of substance P. Prolonged application of capsaicin reversibly depletes stores of substance P, and possibly other neurotransmitters, from sensory nerve endings. This reduces or abolishes the transmission of painful stimuli from the peripheral nerve fibres to the higher centres.

In clinical studies of patients with post-herpetic neuralgia, diabetic neuropathy or osteoarthritis, adjunctive therapy with topical capsaicin achieved better pain relief than its vehicle in most studies. In a single trial, topical capsaicin demonstrated similar efficacy to oral amitriptyline in patients with diabetic neuropathy.

Topical capsaicin is not associated with any severe systemic adverse effects. However, stinging and burning, particularly during the first week of therapy, is reported by many patients.

Topical capsaicin merits consideration as adjuvant therapy in conditions such as post-herpetic neuralgia, diabetic neuropathy and osteoarthritis, where the pain can be chronic and difficult to treat.

Overview of Pharmacology

Capsaicin is the pungent principle of the hot chilli pepper (Capsicumspp.). On initial application capsaicin appears to cause the selective stimulation of afferent C fibres and release of substance P and other neuropeptides. This is responsible for the initial algesic effect associated with topical capsaicin use. Continued application causes depletion of substance P from the sensory nerve ending and a long-lasting desensitisation to burning and pain. These effects are reversible on discontinuation of capsaicin.

Little is known about the human pharmacokinetics of topical capsaicin. Data from animal studies suggest that capsaicin is distributed widely and is metabolised in the liver by the mixed function oxidase system to dihydrocapsaicin. It is thought that capsaicin and its metabolites are excreted renally.

Therapeutic Potential

Topical capsaicin, usually given as adjunctive therapy, has been assessed in several randomised vehicle-controlled studies. While many of the studies were double-blind in design, burning and algesia associated with topical capsaicin in many patients makes true blinding difficult. Many measures are available for the assessment of pain but the most credible are those which involve the use of a visual analogue scale (VAS) for either pain relief or pain intensity. Most studies of topical capsaicin used at least one VAS as an assessment parameter.

In most comparative studies, topical capsaicin 0.025 or 0.075% applied 3 to 4 times daily was significantly more effective than its vehicle in relieving the pain associated with post-herpetic neuralgia, osteoarthritis and diabetic neuropathy. Overall, the clinical studies showed mean reductions of VAS scores for pain intensity following capsaicin therapy in 21 to 39%, 16 to 49% and 28 to 55%, respectively, of patients with post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Placebo responses were high in all conditions. In a single trial, topical capsaicin 0.075% demonstrated similar efficacy to oral amitriptyline 25 to 125 mg/day in patients with diabetic neuropathy.


Topical capsaicin is associated with a low incidence of systemic adverse events. Coughing, a known pharmacological effect of capsaicin, occurs in up to 5% of patients. However, application of capsaicin to the skin causes burning, erythema or stinging in 40 to 70% of patients. While this effect is localised and diminishes with time, it can cause withdrawal from treatment in up to 30% of patients. Coadministration of lidocaine 5% ointment may help in some cases.

Dosage and Administration

Topical capsaicin is available in 2 strengths, 0.025 and 0.075%. Both preparations are currently indicated for use in neuralgias (e.g. post-herpetic neuralgia and diabetic neuropathy); the 0.025% preparation is also indicated for use in osteoarthritis and rheumatoid arthritis.

Topical capsaicin should be applied sparingly to the affected area 3 to 4 times daily. Treatment should continue for at least 4 to 6 weeks, as the onset of clinical benefit may be delayed. Transient burning usually occurs following administration and may be worsened by application schedules of fewer than 3 or 4 times a day.

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Corresponding author

Correspondence to Harriet M. Bryson.

Additional information

Various sections of the manuscript reviewed by: R.D. Altman, Arthritis Division, Department of Medicine, University of Miami, Miami, Florida, USA; D.E. Caughey, Department of Rheumatology, Auckland Hospital, Auckland, New Zealand; B.M. Fusco, Institute of Medical Pathology VI, Headache Center, Università degli Studi di Roma ‘La Sapienza’, Rome, Italy; J.J. Lee, Ronkswood Branch, Worcester Royal Infirmary, Worcester, England; G. Olive, Department of Pharmacology, Hôpital St-Vincent de Paul, Paris, France; AA.F. Sima, Departments of Pathology and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA; R. Tandan, Department of Neurology, University of Vermont College of Medicine, Burlington, Vermont, USA; C.P.N. Watson, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

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Rains, C., Bryson, H.M. Topical Capsaicin. Drugs & Aging 7, 317–328 (1995).

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  • Pain Intensity
  • Capsaicin
  • Herpes Zoster
  • Visual Analogue Scale Score
  • Diabetic Neuropathy