Capsaicin

Capsaicin

Common Names

  • Capsaicin (topical formulations)

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For Patients & Caregivers

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.

  • To improve circulation in the hands and feet
    Lab studies have been conducted, but 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.
  • 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.
  • 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.
  • You are taking cytochrome P4503A4 and 2C19 substrate drugs: Capsaicin may influence how these drugs are metabolized.
  • 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.

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

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For Healthcare Professionals

Zostrix® cream 0.025% & 0.075%; Salonpas® Gel-Patch Hot; Sinus Buster® (homeopathic intranasal spray)
8-methyl-N-vanillyl-6-nonenamide

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 postherpetic neuralgia (8), and was approved for prescription use. Data also show its effectiveness in controlling diabetic peripheral neuropathy (36), and providing sustained relief from heterogenous neuropathic pain (37) and neuropathic pain arising from radiculopathies (38). 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 meaningful use for these conditions in clinical practice (11). Data are also limited in patients with post-mastectomy neuropathy (12).

A preliminary study suggests improved swallowing function in elderly patients with dysphagia when 0.025% capsaicin ointment was applied to the external auditory canal (43). In other reports, several case series suggest topical capsaicin can be effective for cannabis-associated hyperemesis (39) (42). 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). Also, a small study suggests utility of a high-concentration dermal capsaicin patch in relieving pain associated with chemotherapy-induced peripheral neuropathy (CIPN) (40). However, long-term topical application was shown to increase skin carcinogenesis in mice treated with a tumor promoter (18), although such effects may be concentration-dependent (22). Therefore, more studies are needed to clarify the roles of capsaicin in relationship to cancer.

Cayenne peppers, hot sauces containing chili peppers

  • Diabetic neuropathy
  • Headaches
  • Herpes zoster neuropathy
  • HIV neuropathy
  • Muscle pain
  • Osteoarthritis
  • Pruritus
  • Rheumatoid arthritis
  • Spasms

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).

Improved swallowing function in elderly dysphagic patients, particularly glottal closure and cough reflex, was attributed to TRPV1-mediated aural stimulation of vagal Arnold’s nerve with capsaicin ointment (43). 

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). Further exploration of caspaicin-induced apoptosis, in glioma cells, found inhibition of autophagy to be a likely contributor (34). Interestingly, capsaicin was also shown to induce autophagy by enhancing the levels of autophagy markers LC3-II and Atg5, increasing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis in human nasopharyngeal carcinoma cells (41).

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).

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).

Common (over-the-counter topical): Burning, urticaria and contact dermatitis; mild to moderate coughing (6) (12); pain and pruritus at the application site (40).
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).
Application site burns: 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).

  • ACE inhibitors: Topical capsaicin induced cough in a patient taking ACE inhibitors (33).
  • Cytochrome P450 CYP2C19 substrates: Capsaicin inhibits CYP2C19 and can affect the intracellular concentration of drugs metabolized by this enzyme (35).
  • Cytochrome P450 CYP3A4 substrates: Capsaicin induces CYP3A4, which may increase the clearance of substrate drugs when used concomitantly (35).

  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/committeesmeetingmateri…. 2012. Accessed October 20, 2015.

  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. Accessed October 20, 2015.

  33. Hakas JF, Jr. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy. Oct 1990;65(4):322-323.

  34. Liu YP, Dong FX, Chai X, Zhu S, Zhang BL, Gao DS. Role of Autophagy in Capsaicin-Induced Apoptosis in U251 Glioma Cells. Cell Mol Neurobiol. 2015 Sep 9. [Epub ahead of print]

  35. Zhu HD, Gu N, Wang M, Kong HR, Zhou MT. Effects of capsicine on rat cytochrome P450 isoforms CYP1A2, CYP2C19, and CYP3A4. Drug Dev Ind Pharm. 2015 Nov;41(11):1824-8.

  36. van Nooten F, Treur M, Pantiri K, Stoker M, Charokopou M. Capsaicin 8% Patch Versus Oral Neuropathic Pain Medications for the Treatment of Painful Diabetic Peripheral Neuropathy: A Systematic Literature Review and Network Meta-analysis. Clin Ther. 2017 Apr;39(4):787-803.e18.

  37. Mankowski C, Poole CD, Ernault E, et al. Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study. BMC Neurol. 2017 Apr 21;17(1):80.

  38. Baron R, Treede RD, Birklein F, et al. Treatment of painful radiculopathies with capsaicin 8% cutaneous patch. Curr Med Res Opin. 2017 Aug;33(8):1401-1411.

  39. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017 Sep;55(8):908-913.

  40. Filipczak-Bryniarska I, Krzyzewski RM, Kucharz J, et al. High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience. Med Oncol. 2017 Aug 17;34(9):162.

  41. Lin YT, Wang HC, Hsu YC, Cho CL, Yang MY, Chien CY. Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway. Int J Mol Sci. 2017 Jun 23;18(7). pii: E1343.

  42. Graham J, Barberio M, Wang GS. Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series. Pediatrics. Dec 2017;140(6).

  43. Kondo E, Jinnouchi O, Nakano S, et al. Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: A randomized, placebo-controlled, double-blind, comparative study. Clin Interv Aging. 2017;12:1921-1928.

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