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.
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.
This is a preview of subscription content, access via your institution.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Kuffler SW, Nicholls JG, Martin AR. From neuron to brain. 2nd ed. Sunderland, USA: Sinauer Associates Inc. Publishers, 1984
Iversen LL. Nonopioid neuropeptides in mammalian CNS. Annu Rev Pharmacol Toxicol 1983; 23: 1–27
Rumsfield JA, West DP. Topical capsaicin in dermatologic and peripheral pain disorders. DICP 1991 Apr; 25: 381–7
Watson CPN. Topical capsaicin as an adjuvant analgesic. J Pain Symptom Manage 1994 Oct; 9: 425–33
Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations. Pharmacol Rev 1986 Sep; 38: 179–226
Dray A. Therapeutic potential of capsaicin-like molecules: mechanism of action of capsaicin-like molecules on sensory neurons. Life Sci 1992; 51: 1759–65
Ritchie JM, Greene NM. Local anesthetics. In: Gilman AG, Rall TW, Nies AS, et al., editors. Goodman & Gilman’s The Pharmacological basis of therapeutics. 8th ed. Vol. 1. New York: McGraw-Hill, Inc, 1992
Fitzgerald M. Capsaicin and sensory neurones - a review. Pain 1983 Feb; 15: 109–30
Bjerring P, Arendt-Nielsen L. Use of a new argon laser technique to evaluate changes in sensory and pain thresholds in human skin following topical capsaicin treatment. Skin Pharmacol 1989; 2: 162–7
Carter RB. Topical capsaicin in the treatment of cutaneous disorders. Drug Dev Res 1991; 22 (2): 109–23
Kenins P. Responses of single nerve fibres to capsaicin applied to the skin. Neurosci Lett 1982 Mar 17; 29: 83–8
Gamse R, Petsche U, Lembeck F, et al. Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin. Brain Res 1982 May 13; 239: 447–62
Dray A. Neuropharmacological mechanisms of capsaicin and related substances. Biochem Pharmacol 1992 Aug 18; 44: 611–5
Weisman MH, Hagaman C, Yaksh TL. Preliminary findings on the role of neuropeptide suppression by topical agents in the management of rheumatoid arthritis. Semin Arthritis Rheum 1994 Jun; 23 Suppl. 3: 18–24
Monsereenusorn Y. Subchronic toxicity studies of capsaicin and capsicum in rats. Res Commun Chem Pathol Pharmacol 1983; 41(1): 95–110
Spina D, McKenniff MG, Coyle AJ, et al. Effect of capsaicin on PAF-induced bronchial hyperresponsiveness and pulmonary cell accumulation in the rabbit. Br J Pharmacol 1991 May; 103: 1268–74
Biesbroeck R, Bril V, Hollander P, et al. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy. Adv Ther 1995 Mar/Apr; 12(2): 111–20
Bowsher D. Post-herpetic neuralgia in older patients: incidence and optimal treatment. Drugs Aging 1994; 5: 411–8
Lee JJ, Gauci CAG. Postherpetic neuralgia: current concepts and management. Br J Hosp Med 1994; 52: 565–70
Jolleys JV. Treatment of shingles and post-herpetic neuralgia [editorial]. BMJ 1989; 298: 1537–8
Peikert A, Hentrich M, Ochs G. Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course. J Neurol 1991 Dec; 238: 452–6
Srebrnik A, Brenner S. Capsaicin in the relief of postherpetic neuralgia. J Dermatol Treat 1992 Jan; 2: 147–8
Bernstein JE, Korman NJ, Bickers DR, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989; 21: 265–70
Drake HF, Harries AJ, Gamester RE, et al. Randomised double-blind study of topical capsaicin for treatment of post-herpetic neuralgia. Pain 1990; 58 Suppl. 5: S58
Watson CPN, Tyler KL, Bickers DR, et al. A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther 1993 May-Jun; 15: 510–26
Watson CP, Evans RJ, Watt VR. Post-herpetic neuralgia and topical capsaicin. Pain 1988 Jun; 33: 333–40
Watson CPN, Evans RJ, Watt VR, et al. Post-herpetic neuralgia: 208 cases. Pain 1988; 35: 289–97
Scheffler NM, Sheitel PL, Lipton MN. Treatment of painful diabetic neuropathy with capsaicin 0.075%. J Am Podiatr Med Assoc 1991 Jun; 81: 288–93
Capsaicin Study Group, Donofrio P, Walker F, et al. Treatment of painful diabetic neuropathy with topical capsaicin. A multi-center, double-blind, vehicle-controlled study. Arch Intern Med 1991 Nov; 151: 2225–9
Chad DA, Aronin N, Lundstrom R, et al. Does capsaicin relieve the pain of diabetic neuropathy? Pain 1990 Sep; 42: 387–8
Tandan R, Lewis GA, Krusinski PB. Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. Diabetes Care 1992 Jan; 15: 8–14
Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992 Feb; 15: 159–65
Altman RD, Aven A, Holmburg CE, et al. Capsaicin cream 0.025% as monotherapy for osteoarthritis: a double-blind study. Semin Arthritis Rheum 1994 Jun; 23 Suppl. 3: 25–33
Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 1991 May-Jun; 13: 383–95
McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol 1992 Apr; 19: 604–7
Schnitzer T, Morton C, Coker S. Topical capsaicin therapy for osteoarthritis pain: achieving a maintenance regimen. Semin Arthritis Rheum 1994 Jun; 23 Suppl. 3: 34–40
Watson CPN, Evans RJ. The postmastectomy pain syndrome and topical capsaicin: a randomized trial. Pain 1992 Dec; 51: 375–9
Epstein JB, Marcoe JH. Topical application of capsaicin for treatment of oral neuropathic pain and trigeminal neuralgia. Oral Surg Oral Med Oral Pathol 1994 Feb; 77: 135–40
Fusco BM, Alessandri M. Analgesic effect of capsaicin in idio-pathic trigeminal neuralgia. Anesth Analg 1992 Mar; 74: 375–7
Wallengren J, Klinker M. Successful treatment of notalgia pares-thetica with topical capsaicin: vehicle-controlled, double-blind, crossover study. J Am Acad Dermatol 1995 Feb; 32 (Part 1): 287–9
McCarty DJ, Csuka M, McCarthy G. Treatment of pain due to fibromyalgia with topical capsaicin: a pilot study. Semin Arthritis Rheum 1994 Jun; 23 Suppl. 3: 41–7
Mathias BJ, Dillingham TR, Zeigler DN, et al. Topical capsaicin for chronic neck pain: a pilot study. Am J Phys Med Rehab 1995 Jan/Feb; 74(1): 39–44
Wist E, Risberg T. Topical capsaicin in treatment of hyperalgesia, allodynia and dysesthetic pain caused by malignant tumour infiltration of the skin. Acta Oncol 1993; 32(3): 343
Sinoff SE, Hart MB. Topical capsaicin and burning pain [letter]. Clin J Pain 1993 Mar; 9: 70–3
Muhiddin KA, Gallen IW, Harries S, et al. The use of capsaicin cream in a case of erythromelalgia. Postgrad Med J 1994 Nov; 70: 841–3
Cheshire WP, Snyder CR. Treatment of reflex sympathetic dystrophy with topical capsaicin M case report. Pain 1990 Sep; 42: 307–11
Morgenlander JC, Hurwitz BJ, Massey EW. Capsaicin for the treatment of pain in Guillain-Barre syndrome. Ann Neurol 1990 Aug; 28: 199
Wagstaff AJ, Faulds D, Goa KL. Aciclovir: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47(1): 153–205
Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86
Sima AAF, Greene DA. Diabetic neuropathy in the elderly. Drugs Aging 1995; 6: 125–35
Pfeifer MA, Ross DR, Schrage JP, et al. A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy. Diabetes Care 1993 Aug; 16: 1103–15
Deal CL. The use of topical capsaicin in managing arthritis pain: a clinician’s perspective. Semin Arthritis Rheum 1994 Jun; 23 Suppl. 3: 48–51
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.
About this article
Cite this article
Rains, C., Bryson, H.M. Topical Capsaicin. Drugs & Aging 7, 317–328 (1995). https://doi.org/10.2165/00002512-199507040-00007
- Pain Intensity
- Herpes Zoster
- Visual Analogue Scale Score
- Diabetic Neuropathy