Acute pain mechanisms

After injury, local release of neuroactive substances causes sensitization of peripheral nociceptors or the development of ongoing discharge. The resu lting sustained afferent drive causes the spinal release of amino acid neur otransmitters and peptide neuromodulators. Maintained afferent C fiber acti vation initiates processes that increase the fixed ratio of the afferent ac tivity and dorsal horn cell responses, which causes a centrally mediated hy peralgesia; thresholds of cells are decreased, outputs are increased, and r eceptive field size is enhanced. The pharmacology of these various changes is described in this article. Interactions of descending modulatory systems -turned on by the increased nociceptive input-opiate analgesia, and the dev elopment of tolerance also are discussed.