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Last Update: May 23, 2023.

Continuing Education Activity

Capsaicin is a chili pepper extract, genus Capsicum, with analgesic properties. Since its discovery, it is used as a homeopathic remedy to treat burning pain using the concept of "treating like with like" or counter-irritant. Since the first reports, various preparations of capsaicin are used to treat various chronic painful conditions. Systematic reviews have shown that capsaicin is efficacious in treating a variety of conditions. This activity reviews the mechanism of action, indications, and latest research pertinent for clinicians and other interprofessional team members in the clinical setting.


  • Identify the purported indications for using capsaicin.
  • Review the mechanism of action of capsaicin.
  • Summarize the potential adverse effects of capsaicin.
  • Explain interprofessional team strategies for improving care coordination and communication to determine the appropriateness of capsaicin in the clinical setting.
Access free multiple choice questions on this topic.


Capsaicin was first isolated in 1816 by Christian Bucholz. Capsaicin is a chili pepper extract, genus Capsicum, with analgesic properties. Its chemical composition was first determined in 1919. They explained the biosynthetic pathway in the 1960s. Since its discovery, it is used as a homeopathic remedy to treat burning pain using the concept of "treating like with like" or counter-irritant. The first reports of its pain-relieving properties appeared in the mid-1850s as a recommendation to use it for parts of the body that burn or itch. Since the first reports, one uses various preparations of capsaicin to treat a variety of chronic painful conditions. Systematic reviews have shown that capsaicin is efficacious in treating a variety of conditions, including:

  • Nondiabetic neuropathic pain[1]
  • Postherpetic neuralgia[2]
  • Osteoarthritis
  • Chronic musculoskeletal pain[3]
  • Post-mastectomy pain syndrome
  • Burning mouth syndrome
  • Overactive bladder
  • Gastropathy
  • Postoperative nausea and vomiting
  • Pruritus[4]
  • Pruritus ani
  • Postoperative sore throat
  • Improving cough reflex sensitivity in patients with a history of dysphagia and other swallowing related disorders[5]
  • Chemotherapy- and radiotherapy-induced mucositis.

It is important to note that manufacturers have sponsored many of the studies examining the benefits of capsaicin. They often prescribe the agent for many other disorders with little to no supporting evidence. There is little scientific proof it works as a weight-loss agent or lowers blood sugar although more studies need to be done to evaluate its total effect on delaying obesity-related metabolic syndrome.[6][7][8]

Mechanism of Action

Capsaicin, a member of the vanilloid family, is a group of compounds that possess a vanillyl group. It binds as an agonist to vanilloid receptor subtype 1 (TRPV1 - transient receptor potential V1), which is an ion channel type trans-membrane receptor. The TRPV1 receptor also is stimulated by temperature changes, physical abrasion, pH changes, and endogenous lipids. When activated, it starts a depolarization cascade that allows the influx of sodium and calcium ions. TRPV1 receptors are found on C- and A-delta fibers in the nociceptive sensory pathway. When depolarization occurs along fibers, signals propagate into the spinal cord to the brain. 

Capsaicin reduces pain transmission by desensitizing the sensory afferent axons. This phenomenon occurs due to the high permeability of the TRPV1 channels for calcium ions. This excess influx of calcium causes loss of mitochondrial function (as well as other cellular organelles) and thus renders the afferent nerve fiber inoperant.[9]

As these nerve fibers lose functionality, all of the mediators produced within these fibers will also show a marked decrease. One of these substances is a well-known potent local pain mediator, substance P. 

Constant usage of capsaicin further promotes calcium influx into more of these nociceptive nerve fibers. This promotes preformed substance P release during the first applications, which causes initial neurogenic inflammation, but after repeated application, capsaicin depletes the neuron of substance P, and the further inoperability of the cell prevents it from forming more of this pain chemo-mediator.

An alternative mechanism of analgesia is suggested by studies using a potent capsaicin analog, resiniferatoxin. Activation of TRPV1 receptors by resiniferatoxin (RTX) results in a sustained rise in free intracellular calcium levels, which leads to calcium-induced cytotoxicity and the selective death of cells bearing TRPV1 receptors. RTX produced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons in cultures of human dorsal root ganglion, but adjacent non-TRPV1 bearing neurons were not affected.[10] The authors of the study suggested that nociceptive neuronal or nerve terminal deletion may be an effective strategy for pain management.


Capsaicin is administered in many forms such as low-concentration creams, lotions, patches, intradermal injections, oral formulations, subcutaneous injections, intravenous, films, microemulsions, liposomes, and nanotechnology-derived drug delivery systems.

Adverse Effects

The more common potential adverse reactions and events with topical patch administration include local erythema, local pain, local pruritus, local edema, local swelling, local dryness, hypertension, papules, pruritus, nausea, vomiting, nasopharyngitis, sinusitis, bronchitis.

The more rare complications include abnormal skin odor, cough, dizziness, dysgeusia, headaches, hypesthesia, peripheral edema, peripheral sensory neuropathy, and throat irritation.


Some studies have reported relative contraindication in patients with asthma, as they have greater sensitivity to capsaicin. It is presumed that there is increased TRPV1 activity in asthmatics with an increase in endovanilloids in the airways. There are, however, no reported absolute contraindications to the use of capsaicin.


Therapeutic index for topical and oral capsaicin has not been well studied; however, it is known that exposure to high doses, above 100 mg per kg body weight, of capsaicin for a prolonged time can cause peptic ulcers, enhance breast cancer metastasis, and accelerate the development of prostate, stomach, duodenal, and liver cancer. Also, it is advised to not apply it immediately before or after activities such as bathing, swimming, sunbathing, or strenuous exercise and to avoid getting it on mucous membranes or eyes.


From a review of the literature, it appears the acute toxicity of capsaicin is determined only in animal species. A study in mice has shown that application of capsaicin based on LD50 values greater than 9 mg/kg (subcutaneous) or 190 mg/kg (by mouth), the likely mechanism of toxicity involves respiratory paralysis. There is no known reported case of an overdose in humans, and there is no known antidote.

Acute Toxicity

Capsaicin is a potent irritant, and if exposed to the mucous membranes, it can cause severe irritation, pain, and burning. When it gets in the eye, capsaicin can cause prolonged burning pain with tearing, photophobia, and blurry vision. When inhaled, it can cause dry coughing spells, wheezing, and dyspnea.

Most people who present to the emergency department after acute exposure to capsaicin complain of burning pain on the skin. Children have reported side effects of nausea, vomiting, diarrhea, and abdominal cramps.

Some people who have used capsaicin to lose weight have presented to the emergency department with profuse diaphoresis and chest pain. In these patients, reports of myocardial ischemia have been reported. 

If acute exposure has occurred, first remove the patient from further exposure. All contaminated clothing should be removed and placed in an airtight container. If the eyes or nose have been exposed, one should bath the mucous membrane with oils like petroleum jelly or vegetable oil. To relieve the abdominal symptoms, polyethylene glycol or cold milk has been recommended. Skin exposure can be limited by washing the area with detergent followed by a thorough rinse with water. Just plain water alone is not effective at removing capsaicin from the skin.

If the patient has wheezing, one may need to use intravenous corticosteroids and nebulizer therapy.

It is highly recommended that healthcare workers wear gloves and goggles when handling and applying topical capsaicin on the skin of patients.

Enhancing Healthcare Team Outcomes

Managing drug side effects requires an interprofessional team of healthcare professionals, including clinicians, mid-level practitioners, nurses, and pharmacists. Without proper instruction on use, capsaicin can cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis, and blepharospasm. Proper use of capsaicin under interprofessional guidance can be beneficial to patient outcomes. [Level 5]

Review Questions


Gálvez R, Navez ML, Moyle G, Maihöfner C, Stoker M, Ernault E, Nurmikko TJ, Attal N. Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study. Clin J Pain. 2017 Oct;33(10):921-931. [PubMed: 28872473]
Ostrovsky DA. Single Treatment With Capsaicin 8% Patch May Reduce Pain and Sleep Interference up to 12 Weeks in Patients With Painful Diabetic Peripheral Neuropathy. Explore (NY). 2017 Sep-Oct;13(5):351-353. [PubMed: 28915983]
Campbell BK, Fillingim RB, Lee S, Brao R, Price DD, Neubert JK. Effects of High-Dose Capsaicin on TMD Subjects: A Randomized Clinical Study. JDR Clin Trans Res. 2017 Jan;2(1):58-65. [PMC free article: PMC5576044] [PubMed: 28879245]
Pereira MP, Ständer S. Chronic Pruritus: Current and Emerging Treatment Options. Drugs. 2017 Jun;77(9):999-1007. [PubMed: 28466423]
Ternesten-Hasséus E, Johansson EL, Millqvist E. Cough reduction using capsaicin. Respir Med. 2015 Jan;109(1):27-37. [PubMed: 25468411]
Song JX, Ren H, Gao YF, Lee CY, Li SF, Zhang F, Li L, Chen H. Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice. Front Physiol. 2017;8:602. [PMC free article: PMC5575157] [PubMed: 28890700]
Hirotani Y, Fukamachi J, Ueyama R, Urashima Y, Ikeda K. Effects of Capsaicin Coadministered with Eicosapentaenoic Acid on Obesity-Related Dysregulation in High-Fat-Fed Mice. Biol Pharm Bull. 2017;40(9):1581-1585. [PubMed: 28867743]
Qin Y, Ran L, Wang J, Yu L, Lang HD, Wang XL, Mi MT, Zhu JD. Capsaicin Supplementation Improved Risk Factors of Coronary Heart Disease in Individuals with Low HDL-C Levels. Nutrients. 2017 Sep 20;9(9) [PMC free article: PMC5622797] [PubMed: 28930174]
Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011 Oct;107(4):490-502. [PMC free article: PMC3169333] [PubMed: 21852280]
Gregor DM, Zuo W, Fu R, Bekker A, Ye JH. Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats. Anesthesiology. 2019 Apr;130(4):592-608. [PMC free article: PMC6417946] [PubMed: 30676422]

Disclosure: Andrew Chang declares no relevant financial relationships with ineligible companies.

Disclosure: Alan Rosani declares no relevant financial relationships with ineligible companies.

Disclosure: Judy Quick declares no relevant financial relationships with ineligible companies.

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Bookshelf ID: NBK459168PMID: 29083760


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