title: The mechanisms of action of NSAIDs in analgesia.
abstract: Traditionally, the analgesic action of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained on the basis of their inhibition of the enzymes that synthesise prostaglandins. However, it is clear that NSAIDs exert their analgesic effect not only through peripheral inhibition of prostaglandin synthesis but also through a variety of other peripheral and central mechanisms. It is now known that there are 2 structurally distinct forms of the cyclo-oxygenase enzyme (COX-1 and COX-2). COX-1 is a constitutive member of normal cells and COX-2 is induced in inflammatory cells. Inhibition of COX-2 activity represent the most likely mechanism of action for NSAID-mediated analgesia, while the ratio of inhibition of COX-1 to COX-2 by NSAIDs should determine the likelihood of adverse effects. In addition, some NSAIDs inhibit the lipoxygenase pathway, which may itself result in the production of algogenic metabolites. Interference with G-protein-mediated signal transduction by NSAIDs may form the basis of an analgesic mechanism unrelated to inhibition of prostaglandin synthesis. These is increasing evidence that NSAIDs have a central mechanism of action that augments the peripheral mechanism. This effect may be the result of interference with the formation of prostaglandins within the CNS. Alternatively, the central action may be mediated by endogenous opioid peptides or blockade of the release of serotonin (5-hydroxytryptamine; 5-HT). A mechanism involving inhibition of excitatory amino acids of N-methyl-D-aspartate receptor activation has also been proposed.
authors.affiliation: Department of Anaesthetics, St George's Hospital, London, England.
authors.forename: J N
authors.initials: JN
authors.lastname: Cashman
mesh_terms: D000698:Analgesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008084:Lipoxygenase / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016202:N-Methylaspartate / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D016202:N-Methylaspartate; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases