Health Care Professional Information

Scientific Name
8-methyl-N-vanillyl-6-nonenamide
Common Name

Capsaicin (topical formulations)

Brand Name

Zostrix® cream 0.025% & 0.075%; Salonpas® Gel-Patch Hot; Sinus Buster® (homeopathic intranasal spray)

Clinical Summary

Capsaicin is the active component derived from the fruit of capsicum or cayenne pepper. It has been used in traditional medical systems as a remedy to relieve muscle and arthritic pain and to treat cluster headaches and psoriasis. For these purposes, capsaicin is an active ingredient in some topical creams and nasal sprays. It is also available in a prescription-strength patch. Oral formulations are marketed largely for digestive and circulatory problems, poor appetite, and weight loss. (See Cayenne Pepper)

Studies support benefits of topical low-concentration capsaicin formulations for psoriasis (1), prurigo nodularis (2), and pruritus ani (3). Although topical capsaicin has been included among conditional recommendations for osteoarthritis (4), its utility for rheumatoid arthritis remains inconclusive (5). An older clinical trial shows capsaicin 0.075% cream may control post-surgical pain in cancer patients (6). A case report in a palliative care patient using capsaicin 0.025% for opioid-refractory upper extremity pain also reported benefit (7).

A high-concentration dermal capsaicin patch was shown safe and effective for the treatment of postherpetic neuralgia (8), and was approved for prescription use. However, a subsequent application for HIV-associated neuropathic pain was rejected (9). A recent systematic review cites some benefit for both postherpetic neuralgia and HIV-neuropathy over controls. However, the patch is best used when other therapies have failed due to the small number of patients who may benefit (1 in 8) and unknown risks (10). Low-concentration capsaicin was determined as unlikely to have any meaningful use for these conditions in clinical practice (11). There are also limited data on capsaicin for diabetic and post-mastectomy neuropathy (12).

Only a few small studies suggest intranasal capsaicin of divergent formulations may be helpful for rhinitis (13) (14), and its effectiveness for cluster headaches is unknown (15).

There is continued controversy over whether capsaicin acts as a carcinogen, co-carcinogen, or anti-carcinogen (16) (17) (18). For example, capsaicin has demonstrated chemopreventive and antiproliferative effects against various cell lines including breast (19), bladder (20), prostate cancer cells (21). At the same time, long-term topical application was shown to increase skin carcinogenesis in mice treated with a tumor promoter (18), but such effects may be concentration-dependent (22). Therefore, more studies are needed to clarify the roles of capsaicin in relationship to cancer.

Food Sources

Cayenne peppers, hot sauces containing chili peppers

Purported Uses
  • Diabetic neuropathy
  • Headaches
  • Herpes zoster neuropathy
  • HIV neuropathy
  • Muscle pain
  • Osteoarthritis
  • Pruritus
  • Rheumatoid arthritis
  • Spasms
Mechanism of Action

The analgesic effect of capsaicin is multifactorial. It depolarizes C-fiber polymodal nociceptors (23) (24). This causes the release of substance P, the neurotransmitter that relays pain signals to the brain (25), which causes an initial increase in pain. With repeated application, pain subsides due to the eventual depletion of substance P at the afferent neurons (26). Capsaicin also activates transient receptor potential vanilloid subfamily member 1 (TRPV1, also known as the capsaicin receptor) (27), causing selective and reversible defunctionalization of cutaneous sensory nerve endings expressing TRPV1 (28). Studies on various cancer cell lines have shown that capsaicin demonstrates chemopreventive properties by causing cell-cycle arrest and inducing apoptosis, or by generating reactive oxygen species (ROS) and depolarizing mitochondrial membranes, and through caspase activation (17) (19) (20). Alternatively, the co-carcinogenic effect of capsaicin on chemically-induced skin carcinogenesis is mediated through the epidermal growth factor receptor (EGFR), but not TRPV1 (18).

Pharmacokinetics

General Dermal: Capsaicin is absorbed through the skin and mucous membranes.
High-concentration transdermal patch, 60-minute application (29): In any patient, maximum plasma concentration observed was 17.8 ng/mL. Mean population elimination half-life was 1.64 hours. Mean AUC and Cmax values were 7.42 ng x h/mL and 1.86 ng/mL, respectively.

Warnings

Capsaicin can irritate mucous membranes, the eyes, and broken skin. For all capsaicin creams, gels, and lotions, wear gloves during application and wash hands with soap and water afterwards to avoid spreading the active ingredient to these sensitive areas. Capsaicin use should be considered when encountering adverse cardiovascular effects in the absence of illicit substance use and especially in young patients (30).

Contraindications

Patients with unstable or poorly controlled hypertension or a recent history of cardiovascular or cerebrovascular events, as this may cause an increased risk of adverse cardiovascular effects (8).

Adverse Reactions

Common (over-the-counter topical): Burning, urticaria and contact dermatitis; mild to moderate coughing (6) (12).
Transient (intranasal): Burning sensations, lacrimation, and rhinorrhea (15).

Case Reports
Coronary vasospasm and acute myocardial infarction:
Observed in a 29-year-old man following use of a topical capsaicin patch for 6 days. Improvement was seen after treating symptoms and patch removal (30).
Bilateral acute anterior uveitis: Occurred in a 38-year-old woman 1–2 days after application of an analgesic capsaicin patch for muscular neck pain. Inflammation was controlled within 1 week using topical corticosteroids, and there were no further recurrences over long-term follow-up (31).
Burns at the application site: Cases of serious burns have occurred following use of over-the-counter capsaicin products. In some cases, hospitalization was required. Discontinue use and seek immediate medical attention if pain, swelling, or blistering occur following application (32).

Herb-Drug Interactions

ACE inhibitors: Topical capsaicin induced cough in a patient taking ACE inhibitors (33).

Literature Summary and Critique

Derry S, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;2:CD007393.
This systematic review evaluated studies involving high-concentration (8%) topical capsaicin as a single patch application for chronic neuropathic pain in adults. Scientific database searches included trials up until December 2012 and limited selection criteria to those that were randomized, double-blind, placebo-controlled studies of ≥6 weeks in duration. Data extracted included numbers of participants with pain relief after ≥6 weeks. Risk ratio and numbers needed to treat (NNT) were calculated. First-tier evidence of efficacy was considered to be long-duration pain relief, usually determined from the patient global impression of change (PGIC), most often at 8 and 12 weeks. Second-tier evidence was considered to be average pain scores over Weeks 2–8 and 2–12, and number of participants with ≥30% pain reduction or ≥50% reduction over baseline.

A total of 6 studies involving 2073 participants were reviewed, and found to be of good reporting quality. Of those, 4 studies involved 1272 participants with postherpetic neuralgia, and 2 studies involved 801 participants with HIV-neuropathy. Control for blinding was topical capsaicin 0.04%. At both Week 8 and 12, high-concentration capsaicin showed significant benefit over controls for those reporting to be much or very much better: NNT 8.8 (95% CI 5.3–26) and 7.0 (95% CI 4.6–15), respectively. More participants had average Week 2–8 and Week 2–12 pain intensity reductions ≥30% and ≥50% over baseline with active treatment than controls (NNT 10–12). In one HIV-neuropathy study, Week-12 NNT to be much or very much better was 5.8 (95% CI 3.8–12). Over both HIV-neuropathy studies more participants had average Week 2–12 pain intensity reductions over baseline of ≥30% with active treatment than controls (NNT 11) . Frequency of serious adverse events appeared to be comparable between arms: active treatment, 4.1% vs controls, 3.2%. There were no between-group differences for adverse event withdrawals, although withdrawals were somewhat more common with controls for lack of efficacy.

The reviewers concluded that high-concentration capsaicin generates higher levels of pain relief than controls for chronic neuropathic pain. But because the proportion who benefit is not large, it should likely be used when other therapies have failed, and should not be used repeatedly without substantial documented pain relief, due to unknown risks with repeated applications over long periods.

Cho JH, et al. Efficacy of a 0.1% capsaicin hydrogel patch for myofascial neck pain: a double-blinded randomized trial. Pain Med. 2012;13:965-970.
This double-blind randomized controlled trial evaluated the efficacy of a capsaicin 0.1% hydrogel patch compared with a placebo to treat chronic myofascial neck pain. A total of 61 adults with neck pain lasting ≥3 months and clinically presenting with myofascial pain syndrome were enrolled. All participants were instructed to apply one patch to each side of the neck and shoulder girdle overlying the point of maximal pain for 12 h daily throughout the 4-week study. Each participant completed 5 surveys at baseline, at 2 weeks after start of treatments, and at the conclusion of the 4-week study. Visual analog scale (VAS) was the primary outcome measure. Other measures included the Neck Disability Index (NDI), Beck's Depression inventory (BDI), Short Form 36 Korean version, and Euroqol 5-D. Of those who completed the study (n=57), mean VAS, NDI, and BDI scores were significantly decreased at Weeks 2 and 4 from start of the intervention in both groups, with no significant between-group differences in any of the outcome measures. The authors concluded that subsequent research should discern what effects relate to capsaicin treatment, the trigger point stimulation occurring during patch application, and the placebo effect.

Ellison et al. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol. 1997;15:2974-2980.
In this double-blind crossover study, 99 patients with postsurgical neuropathic pain received 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. Patients were instructed to apply the study or placebo cream to the painful site 4 times daily, and to complete weekly questionnaires for treatment evaluation. During the first 8-week study period, those in the capsaicin-cream arm reported substantially more skin burning, skin redness, and coughing (P<.0001 for each). However, treatment cessation for patient refusal or toxicity was comparable between arms and those using the study cream experienced substantially more pain relief after the first 8 weeks (P=.01), with an average pain reduction of 53% vs 17%. Upon completion of the 16-week study period, patients were asked which 8-week period they felt was most beneficial. Of those who responded (n=60), 60% chose the capsaicin arm, 18% chose the placebo, and 22% chose neither (P=.001). The investigators concluded that despite toxicities, there was significant preference for the study cream to manage postsurgical neuropathic pain in those who expressed an opinion.

Dosage (Inside MSKCC Only)
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References
  1. Ellis CN, Berberian B, Sulica VI, et al. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol. Sep 1993;29(3):438-442.
  2. Stander S, Luger T, Metze D. Treatment of prurigo nodularis with topical capsaicin. J Am Acad Dermatol. Mar 2001;44(3):471-478.
  3. Lysy J, Sistiery-Ittah M, Israelit Y, et al. Topical capsaicin—a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study. Gut. Sep 2003;52(9):1323-1326.
  4. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). Apr 2012;64(4):465-474.
  5. Richards BL, Whittle SL, van der Heijde DM, et al. Efficacy and safety of neuromodulators in inflammatory arthritis: a Cochrane systematic review. J Rheumatol Suppl. Sep 2012;90:28-33.
  6. Ellison N, Loprinzi CL, Kugler J, et al. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol. Aug 1997;15(8):2974-2980.
  7. Turnbull JH, Gebauer SL, Miller BL, et al. Cutaneous nerve transection for the management of intractable upper extremity pain caused by invasive squamous cell carcinoma. J Pain Symptom Manage. Jul 2011;42(1):126-133.
  8. Backonja MM, Malan TP, Vanhove GF, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension. Pain Med. Apr 2010;11(4):600-608.
  9. FDA Advisory Committee. Efficacy and safety of Qutenza in the management of neuropathic pain associated with HIV-associated peripheral neuropathy: Introduction and overview. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/anestheticandanalgesicdrugproductsadvisorycommittee/ucm291588.pdf. 2012.
  10. Derry S, Sven-Rice A, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;2:CD007393.
  11. Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012;9:CD010111.
  12. Derry S, Lloyd R, Moore RA, et al. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2009(4):CD007393.
  13. Van Rijswijk JB, Boeke EL, Keizer JM, et al. Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study. Allergy. Aug 2003;58(8):754-761.
  14. Bernstein JA, Davis BP, Picard JK, et al. A randomized, double-blind, parallel trial comparing capsaicin nasal spray with placebo in subjects with a significant component of nonallergic rhinitis. Ann Allergy Asthma Immunol. Aug 2011;107(2):171-178.
  15. Matharu M. Cluster headache. Clin Evid (Online). 2010;2010.
  16. Bode AM, Dong Z. The two faces of capsaicin. Cancer Res. Apr 15 2011;71(8):2809-2814.
  17. Lin CH, Lu WC, Wang CW, et al. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Altern Med. 2013;13:46.
  18. Hwang MK, Bode AM, Byun S, et al. Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1. Cancer Res. Sep 1 2010;70(17):6859-6869.
  19. Thoennissen NH, O'Kelly J, Lu D, et al. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene. Jan 14 2010;29(2):285-296.
  20. Yang ZH, Wang XH, Wang HP, et al. Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology. Mar 2010;75(3):735-741.
  21. Mori A, Lehmann S, O'Kelly J, et al. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res. Mar 15 2006;66(6):3222-3229.
  22. Yang J, Li TZ, Xu GH, et al. Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma. 2013;60(4):364-372.
  23. Lynn B. Capsaicin: actions on nociceptive C-fibres and therapeutic potential. Pain. Apr 1990;41(1):61-69.
  24. Marsh SJ, Stansfeld CE, Brown DA, et al. The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro. Neuroscience. Oct 1987;23(1):275-289.
  25. Paice JA, Ferrans CE, Lashley FR, et al. Topical capsaicin in the management of HIV-associated peripheral neuropathy. J Pain Symptom Manage. Jan 2000;19(1):45-52.
  26. Nolano M, Simone DA, Wendelschafer-Crabb G, et al. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain. May 1999;81(1-2):135-145.
  27. Sobhan U, Sato M, Shinomiya T, et al. Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands. Cell Tissue Res. Aug 15 2013.
  28. Simpson DM, Brown S, Tobias JK, et al. NGX-4010, a Capsaicin 8% Dermal Patch, for the Treatment of Painful HIV-associated Distal Sensory Polyneuropathy: Results of a 52-Week Open-Label Study. Clin J Pain. Feb 26 2013.
  29. Babbar S, Marier JF, Mouksassi MS, et al. Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain. Ther Drug Monit. Aug 2009;31(4):502-510.
  30. Akcay AB, Ozcan T, Seyis S, et al. Coronary vasospasm and acute myocardial infarction induced by a topical capsaicin patch. Turk Kardiyol Dern Ars. Oct 2009;37(7):497-500.
  31. Bleuel I, Zinkernagel M, Tschopp M, et al. Association of bilateral acute anterior uveitis with a capsaicin patch. Ocul Immunol Inflamm. Oct 2013;21(5):394-395.
  32. U.S. Food and Drug Administration. FDA Drug Safety Communication: Rare cases of serious burns with the use of over-the-counter topical muscle and joint pain relievers. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm318858.htm. 2012.
  33. Hakas JF, Jr. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy. Oct 1990;65(4):322-323.

Consumer Information

How It Works

Bottom Line: Capsaicin is effective in the treatment of psoriasis and may be helpful in relieving some types of joint pain. In prescription doses, it may also be helpful for some types of neuropathic pain.

Capsaicin is the spicy ingredient in hot chili or cayenne peppers. When applied to skin, capsaicin is absorbed and blocks pain signals from getting to the brain. At first, sensitivity and pain may increase, but repeated applications cause substance P (a protein that transmit pain signals) to be used up, which reduces the pain. This requires repeated applications 4 or 5 times daily for a period of at least 4 weeks to be effective. Other uses for capsaicin have been considered, but research is lacking.

Whether capsaicin can protect against or cause cancer is uncertain. More studies are needed to determine how capsaicin actually interacts with cancer cells or aids in their prevention.

Purported Uses
  • To improve circulation in the hands and feet
    Lab studies have found that capsaicin closes up blood vessels in the skin, which would decrease circulation to the hands and feet. Its clinical benefit has yet to be examined in large clinical trials.
  • To relieve nerve pain
    Clinical trials show mixed results for different types of nerve pain. A prescription skin patch was shown to be safe and effective for shingles-related nerve pain. In a small study, an over-the-counter cream was found to be helpful for post-surgical pain in cancer patients. More studies are needed.
  • To relieve muscle pain and muscle spasms
    Lab data show that capsaicin blocks pain signals in nerve fibers, but human data are lacking.
  • To treat osteoarthritis and rheumatoid arthritis
    Data from clinical trials are inconclusive. More research is required.
  • To treat psoriasis
    Data from clinical trials support this use.
  • To treat headaches
    Whether capsaicin can be used to treat headaches is unknown.
Patient Warnings
  • Capsaicin cream can be very irritating to mucous membranes, the eyes, and broken skin. Avoid spreading the cream to sensitive areas, wear gloves to apply, and wash hands with soap and water afterwards.
  • Rare cases of serious burns have occurred following use of capsaicin products. Discontinue use and seek immediate medical attention if pain, swelling, or blistering occurs following use.
Do Not Take If
  • You are taking ACE inhibitors: Capsaicin can increase the incidence of cough associated with this drug.
  • You have poorly controlled blood pressure, heart disease, or other vascular conditions.
Side Effects
  • When applied topically: burning, redness, swelling, itching and coughing.
  • When applied with a nasal spray: Burning sensations, tear production, and nasal mucous discharge.

    Case reports include incidences of:
  • Acute heart attack caused by constricted blood vessels with topical capsaicin patch.
  • Acute eye inflammation and vision problems after using a capsaicin patch for muscular neck pain.
Special Point

Capsaicin cream, when used topically to treat pain, usually takes several weeks of 4 to 5 applications a day to start working.

E-mail your questions and comments to aboutherbs@mskcc.org.