Capsaicin is a natural product of capsicum peppers, it is an active ingredient in many hot foods. When nociceptors- neurons that transmit information regarding tissue damage to pain-processing centers in the spinal cord and brain- come in contact with capsaicin, the neuron gets excited, and there is a perception of pain, and the a local release of inflammatory mediators. These nociceptors get excited by increasing permeability of plasma membrane to cations, but the molecular mechanism explaining this phenomenon is unclear.

Capsaicin is being used in an analgesic agent in the treatment of painful disorders, causing long-term loss of responsiveness because it kills off the nociceptor, or it destroys the peripheral terminals. It was decide that the existence of a receptor site represents the most likely mechanism, because the capsaicin derivative showed structure-function relationships and evoked responses in a dose-dependent manner.

Capsaicin is a powerful and stable alkaloid that can be detected by human taste buds in solutions of ten parts per million. Capsaicin's composition (C18H27NO3) is similar to peperin (C17H19NO3), that gives black pepper its bite. The burning and painful sensations associated with capsaicin result from capsaicin's chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1), which is a ion channel-type receptor. VR1, which can also be stimulated with heat and physical abrasion, permits positively-charged ions (i.e. cations) to pass through the cell membrane and into the cell from outside when activated. The resulting "depolarization" of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same effect that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.

Because of the burning sensation capsaicin is commonly used in food products to give them added spice or heat. The degree of heat found within a food is measured on the Scoville scale. Typically the capsaicin is obtained by using chili peppers as the source. Another common source is hot sauces (which may contain pure capsaicin or chili peppers). These sources are preferred over pure capsaicin for reasons of safety resulting from the lower concentration. Capsaicin is fat-soluble rather than water-soluble, so the drinking of water offers little relief from the burning sensation of excessively spiced food. Eating (unspiced) fatty food (buttered bread, ice-cream etc.) will extract the residual capsaicin from the mouth and relieve the burning.

Capsaicin is used in topical ointments used to relieve the pain of peripheral neuropathy (for example postherpetic neuralgia). 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. The result appears to be that the nerves are overwhelmed from the burning sensation and are unable to report pain for an extended period of time. Capsaicin is approved for use for the symptomatic relief of pain associated with osteoarthritis (pain experienced in and around the joints when they are being used). However, it has been used to treat many other types of neuralgic pain including: Post-herpetic neuralgia: mild to severe pain on the surface of the skin in patients who have just had shingles (herpes zoster). This pain occurs in about 20% of people and can persist for one month or more after the shingles rash heals. Trigeminal neuralgia: disorder of the trigeminal nerve that causes episodes of intense, stabbing, electric shock-like pain in the areas of the face where the nerve endings reach (lips, eyes, nose, scalp, forehead, upper jaw, and lower jaw). Atypical facial pain: facial pain, often described as burning, aching or cramping that occurs on one side of the face, and can extend into the upper neck or back of the scalp. Brachioradial pruritus: an itchy condition of the arms localized to skin near the elbows.

The word capsaicin actually describes a complex of related components named capsaicinoids. Capsaicinoids are the chemical compounds that give chile peppers their bite. Scientists have identified and isolated six naturally occurring members of this fiery family and one synthetic cousin, which is used as a reference gauge for determining the relative pungency of the others. The major capsaicinoids that are contained in the crystalline extract and their percentages are capsaicin (69%), dihydrocapsaicin (22%), and three minor related components: nordihydrocapsaicin (7%), homocapsaicin (1%), and homodihydrocapsaicin (1%).