Acute pain mechanisms

After injury, local release of neuroactive substances causes sensitization of peripheral nociceptors or the development of ongoing discharge. The resulting sustained afferent drive causes the spinal release of amino acid neurotransmitters and peptide neuromodulators. Maintained afferent C fiber activation initiates processes that increase the fixed ratio of the afferent activity and dorsal horn cell responses, which causes a centrally mediated hyperalgesia; thresholds of cells are decreased, outputs are increased, and receptive 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 development of tolerance also are discussed.