Capsaicin is a chemical compound that was first isolated from chili peppers in crystalline form in 1878. Soon after, it was discovered that capsaicin caused a burning sensation in the mucous membranes. In addition, it increased secretion of gastric acid and stimulated the nerve endings in the skin. The chemical structure of capsaicin was partly elucidated in 1919, and in 1930 capsaicin was chemically synthesized. In 1961, substances similar to capsaicin were isolated from chili peppers by Japanese chemists, who named them capsaicinoids. Dihydrocapsaicin (22%), nordihydrocapsaicin (7%), and homocapsaicin (1%) comprise 30% of the total capsaicinoids mixture and have about half the pungency of capsaicin.1
Pepper spray, also known as capsicum spray, is a lachrymatory agent (a chemical compound that irritates the eyes to cause tears, pain, and even temporary blindness) used in crowd control and personal self-defense, including defense against dogs and bears. The active ingredient in pepper spray is oleoresin capsicum (OC) from chili peppers that is extracted in an organic solvent such as ethanol. The solvent is then evaporated, and the waxlike resin is emulsified with propylene glycol to suspend the OC in water. The OC is then pressurized for use in pepper spray.2
Capsaicin is currently used in topical form for postherpetic neuralgia. This medication is also used on the skin to relieve pain in conditions such as arthritis, psoriasis, or diabetic neuropathy. New studies from the American Association for Cancer Research suggest that capsaicin is also able to kill prostate cancer cells by causing them to undergo apoptosis.2
The Scoville Scale
Capsaicin is a remarkable health-promoting substance. But since burning and irritation are common side effects, it may be wise to start using it slowly and build up a tolerance for larger quantities. The Scoville Scale is a tool for measuring the hotness of a chili pepper, as defined by the amount of capsaicin it contains, and is named after its creator, W. Scoville. This tool is also known as the Scoville Organoleptic Test. An alternative method for quantitative analysis uses high-performance liquid chromatography, making it possible to directly measure capsaicinoid content. Some hot sauces use their Scoville rating in advertising as a selling point.2
Current Medical Applications
FDA-labeled indications for capsaicin are arthritis and musculoskeletal pain, and FDA-nonlabeled indications are neuropathy postoperative complications, postherpetic neuralgia, postoperative nausea and vomiting (prophylaxis), and psoriasis.
Capsaicin is currently used in topical ointments to relieve the pain of peripheral postherpetic neuralgia caused by shingles. It may be used in concentrations of between 0.025% and 0.075%. Capsaicin may also be used as a cream for the temporary relief of minor aches and joint pain associated with arthritis, simple backache, strains, and sprains. The treatment typically involves the application of a topical anesthetic until the area is numb. Then, the capsaicin is applied by a therapist wearing rubber gloves and a face mask. The capsaicin remains on the skin until the patient starts to feel the "heat," at which point it is promptly removed. Capsaicin is also available in large bandages that can be applied to the back.2
Mechanism of Action
The exact mechanism of action of topical capsaicin has not been fully elucidated. Capsaicin is a neuropeptide-active agent that affects the synthesis, storage, transport, and release of substance P, which is believed to be the principal chemical mediator of pain impulses from the peripheral nervous system to the central nervous system. In addition, substance P has been shown to be released into joint tissues, where it activates inflammatory intermediates that are involved with the development of rheumatoid arthritis. Capsaicin renders skin and joints insensitive to pain by depleting and preventing reaccumulation of substance P in peripheral sensory neurons. With the depletion of substance P in the nerve endings, local pain impulses cannot be transmitted to the brain.
Capsaicin selectively binds to a protein known as TRPV1, which resides on the membranes of pain- and heat-sensing neurons. TRPV1 is a heat-activated calcium channel, with a threshold to open between 37°C and 45°C (37°C is normal body temperature). When capsaicin binds to TRPV1, it causes the channel to lower its opening threshold, thereby opening it at temperatures less than the body's temperature, which is why capsaicin is linked to the sensation of heat. As mentioned earlier, prolonged activation of these neurons by capsaicin depletes presynaptic substance P, one of the body's neurotransmitters for pain and heat, and prevents reaccumulation. Neurons that do not contain TRPV1 are unaffected; this causes extended numbness following surgery, and the patient does not feel pain as the capsaicin is applied under anesthesia.
With chronic exposure to capsaicin, neurons are depleted of neurotransmitters, and this leads to a reduction in sensation of pain and a blockage of neurogenic inflammation. If capsaicin is removed, the neurons recover.3
Adlea, which is in phase III trials, is a TRPV1 agonist based on capsaicin. Administered locally to the site of pain, Adlea has been shown to provide site-specific pain relief by binding to TRPV1 receptors, which are found predominantly on C-fiber neurons.
Long-lasting pain is transmitted in the body by C-fiber neurons and is associated with longer term, dull, aching, throbbing pain. In contrast, A-fiber neurons transmit immediate pain such as that experienced milliseconds after slamming your finger in a door or touching a hot surface. Because Adlea acts primarily on C-fiber neurons, it has not been shown to have an adverse effect on normal sensations such as temperature or touch.
Capsaicin and Prostate Cancer
It has been reported that capsaicin down-regulates the expression of not only prostate-specific antigen (PSA), but also androgenic receptors, the steroid-activated proteins that control expression of specific growth-related genes.
The American Association for Cancer Research reports that capsaicin is able to kill prostate cancer cells by causing them to undergo apoptosis. Capsaicin inhibited the activity of NF-kappa beta, a molecular mechanism that participates in the pathways leading to apoptosis in many cell types. Capsaicin also affected the tumors formed by human prostate cancer cell cultures grown in mouse models; results showed that treated tumors were about one-fifth the size of untreated tumors.4
Promoter assays also showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA enhancer, even in the presence of exogenous androgenic receptors (ARs) in LNCaP cells. This suggests that capsaicin inhibited the transcription of PSA not only via down-regulation of AR expression, but also by a direct inhibitory effect.
Although capsaicin reduced the amount of AR that the tumor cells produced, it did not interfere with normal movement of AR into the nucleus of the cancer cells, where the steroid receptor acts to regulate androgen target genes.5
Risks and Precautions
While capsaicin is reported to have benefits in increasing metabolism by burning fats, relieving topical pain, and reducing insulin spikes in diabetes, it 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.
The primary treatment is removal from exposure. Contaminated clothing should be removed and placed in airtight bags. Capsaicin could be washed off the skin using soap or other detergents or rubbed off with oily compounds such as vegetable oil, petroleum jelly, or polyethylene glycol. Plain water, vinegar, and topical antacid suspensions are ineffective in removing capsaicin.
Burning and pain can be relieved by cooling from ice, cold water, cold surfaces, or air from wind or a fan. In severe cases, eye burn might be treated with topical ophthalmic anesthetics. Mucous membrane burn might be treated with lidocaine gel, and capsaicin-induced asthma might be treated with nebulized bronchodilators, oral antihistamines, or corticosteroids.6
1.Nelson AJ, Ragan BG, Bell GW, et al. Capsaicin-based analgesic balm decreases pressor responses evoked by muscle afferents. Med Sci Sports Exerc. 2004;36(3):444-450.
2. Murray MT, Pizzorno JE Jr. Capsicum frutescens (cayenne pepper). In: Pizzorno JE Jr, Murray MT, eds. Textbook of Natural Medicine. 3rd ed. Edinburgh, Scotland: Churchill Livingstone; 2006:803-807.
3. Dray A. Mechanism of action of capsaicin-like molecules on sensory neurons. Life Sci. 1992;51(23):1759-1765.
4. Mori A, Lehmann S, O'Kelly J, et al. Capsacin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutent prostate cancer cells. Cancer Res. 2006;66(6):3222-3229.
5. American Association for Cancer Research (2006). Pepper component hot enough to trigger suicide in prostate cancer cells. www.eurekalert.org/pub_releases/2006-03/aafc-pch031306.php.
6. Benefits of capsaicin. www.flamingmouth.com/Benefits_of_Capsaicin/html.
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