Capsaicin is responsible for the irritating effect of red pepper when applied to the skin or ingested. This is due to its ability to release substance P (the "P" stands for "pain") from nerve cells, which in turn results in irritation and pain. However, once substance P is released, capsaicin works to block its reuptake. The net result is that repeated applications of capsaicin deplete substance P from small nerve fibers, thereby eventually blocking the pain sensation. A similar occurrence happens with the ingestion of cayenne pepper in that the more frequently it is consumed, the greater the tolerance.
Capsaicin-containing creams and gels are available as FDA-approved topical treatments for arthritis and pain such as that seen in diabetic neuropathy. Clinical studies demonstrate that capsaicin products applied topically can produce impressive results in cases of psoriasis, rheumatoid arthritis, and post herpes pain (post herpetic neuralgia). Topical capsaicin preparations have been shown to be an effective treatment for cluster headaches and osteoarthritis pain.
Cayenne pepper exerts beneficial effects internally as well. Perhaps most important are its effects of stimulating and enhancing digestion. A recent New England Journal of Medicine study found that daily doses of red pepper significantly reduced symptoms of indigestion in individuals with frequent indigestion (functional dyspepsia). In this placebo-controlled trial, thirty men and women with frequent indigestion were randomly assigned to receive either 2.5 g of red pepper powder thrice a day before meals or a placebo for five weeks. Each day during the trial, the study participants scored and recorded the severity of their symptoms, such as stomach pain, stomach fullness, nausea, and changes in appetite.