Capsaicin produces pain by selectively activating polymodal nociceptive neurons. This involves a membrane depolarization and the opening of a unique, cation-selective, ion channel which can be blocked by ruthenium red. The capsaicin-induced activation is mediated by a specific membrane receptor which can be selectively and competitively antagonised by capsazepine. Repetitive administrations of capsaicin produces a desensitization and an inactivation of sensory neurons. Several mechanisms are involved. These include receptor inactivation, block of voltage activated calcium channels, intracellular accumulation of ions leading to osmotic changes and activation of proteolytic enzyme processes. Systemic and topical capsaicin produces a reversible antinociceptive and antiinflammatory action after an initial undesirable algesic effect. Capsaicin analogues, such as olvanil, have similar properties with minimal initial pungency. Systemic capsaicin produces antinociception by activating capsaicin receptors on afferent nerve terminals in the spinal cord. Spinal neurotransmission is subsequently blocked by a prolonged inactivation of sensory neurotransmitter release. Local or topical application of capsaicin blocks C-fibre conduction and inactivates neuropeptide release from peripheral nerve endings. These mechanisms account for localized antinociception and the reduction of neurogenic inflammation respectively.