Irritant Chemicals
Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.13 Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.14 Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.15
Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.1 Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.
Medicinal Use
On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,5 postherpetic neuralgia,6 psoriasis,16 and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,17 fibromyalgia,18 migraines,14 cluster headaches,9 and HIV-associated distal sensory neuropathy.5
Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.19 The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.11 Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.20,21
Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.22 The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.23
Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.27 Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.
Final Thoughts
Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.