Capsaicin

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Capsaicin

Common Names

  • Capsaicin (topical formulations)

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

Capsaicin is the chemical in chili or cayenne peppers that makes them spicy. It has been used in traditional medicine to help with joint and muscle pain.

Capsaicin is added to skin creams, gels, ointments, lotions, and comes as a prescription-strength pain patch for relieving muscle pain. It is also added to nasal sprays to relieve chronic sneezing or a congested, runny nose.  

What is it used for?

Capsaicin is used to:

  • Reduce nerve pain
  • Help with pain caused by strained or sprained muscle
  • Relieve pain caused by arthritis
  • Treat psoriasis (skin disease that causes red, itchy scaly patches that mostly appear on your scalp, elbows, knees, and lower back)

Capsaicin also has other uses that haven’t been studied by doctors to see if they work.

It’s generally safe to eat foods with capsaicin, such as chili or cayenne peppers, but talk with your healthcare providers before taking capsaicin supplements. Herbal supplements are stronger than the herbs you would use in cooking. They can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using capsaicin on your skin may include:

  • Burning
  • Redness
  • Swelling
  • Dryness
  • Soreness
  • Itching
  • Cough
  • Runny eyes and nose when using nasal spray with capsaicin
What else do I need to know?
  • Wear gloves before applying capsaicin gels, creams, ointments, or lotions on your skin. After applying, wash your hands with soap and water so you don’t get it into your eyes or other sensitive areas of your body.
  • If you’re using capsaicin for arthritis in your hands, follow the instructions on the label for how long you should leave it on.
  • Don’t use capsaicin when your skin is irritated, infected, or when you have a wound.
  • Talk to your healthcare provider before using capsaicin if you have high blood pressure, heart conditions, or blood vessel problems in the brain. Capsaicin may make these conditions worse.
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For Healthcare Professionals

Brand Name
Zostrix® cream 0.025% & 0.075%; Salonpas® Gel-Patch Hot; Sinus Buster® (homeopathic intranasal spray)
Scientific Name
8-methyl-N-vanillyl-6-nonenamide
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). It is also conditionally recommended for osteoarthritis  (4), and a meta-analysis suggests it may be as effective as topical NSAIDs for osteoarthritic pain (44), but 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 suggest it is superior to pregabalin (45), and effective for diabetic peripheral neuropathy (36), heterogenous neuropathic pain (37), and neuropathic pain arising from radiculopathies (38), but not HIV-associated neuropathic pain (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.

Food Sources

Cayenne peppers, hot sauces containing chili peppers

Purported Uses
  • Arthritis
  • Neuropathy
  • Muscle pain
  • Pruritus
  • Headaches
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).

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).

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); 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).

Herb-Drug Interactions
  • ACE inhibitors: Topical capsaicin induced cough in a patient taking ACE inhibitors (33).
  • CYP450 2C19 substrates: In animal models, capsaicin inhibits CYP2C19 and can affect the intracellular concentration of drugs metabolized by this enzyme (35). Clinical relevance has yet to be determined.
  • CYP450 3A4 substrates: In animal models, capsaicin induces CYP3A4, which may increase the clearance of substrate drugs when used concomitantly (35). Clinical relevance has yet to be determined.
Dosage (OneMSK Only)
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. Clifford DB, Simpson DM, Brown S, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. Feb 1 2012;59(2):126-133.
  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. BMJ Clin Evid. 2010 Feb 9;2010:1212. 
  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. 2014 Feb;30(2):134-42
  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 28, 2020.
  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. 2016 Jul;36(5):737-43
  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.
  44. Persson MSM, Stocks J, Walsh DA, et al. The relative efficacy of topical non-steroidal anti-inflammatory drugs and capsaicin in osteoarthritis: a network meta-analysis of randomised controlled trials. Osteoarthritis Cartilage. Dec 2018;26(12):1575-1582.
  45. Cruccu G, Nurmikko TJ, Ernault E, et al. Superiority of capsaicin 8% patch versus oral pregabalin on dynamic mechanical allodynia in patients with peripheral neuropathic pain. Eur J Pain. Apr 2018;22(4):700-706.
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