- Capsaicin (topical formulations)
For Patients & Caregivers
How It Works
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. Oral formulas are marketed largely for digestive and circulatory problems, poor appetite, and weight loss (See Cayenne Pepper).
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 relieve nerve pain
Clinical trials show mixed results for different types of nerve pain with a prescription patch. More studies are needed.
To relieve muscle pain and muscle spasms
Lab data show that capsaicin blocks pain signals, but human data are lacking.
To treat arthritis
Data from trials suggest some benefit for osteoarthritis. Additional studies are needed.
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.
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.
- You are taking CYP450 3A4 and 2C19 substrate drugs: In animal studies, capsaicin influenced how these drugs were metabolized. Clinical relevance has yet to be determined.
- When applied topically: burning, redness, swelling, itching and coughing.
When applied with a nasal spray: Burning sensations, tear production, and nasal mucous discharge.
- 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.
For Healthcare Professionals
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.
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).
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).
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).
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).
- 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.