Prostaglandins, Aspirin, and Analgesia

The mechanism of action of aspirin and similar drugs and the role of prostaglandins in the pathogenesis of inflammation are being actively studied. That prostaglandins have a role in inflammation seems obvious from their recovery in a number of exudates produced by experimental inflammatory stimuli. Therefore, drugs such as aspirin, indomethacin, and phenylbutazone probably act to block prostaglandin synthesis and relieve symptoms. Similarly, the antipyretic actions of these antiinflammatory agents is explained by the finding that some prostaglandins are potent pyrogens. It has also been suggested that inhibition of prostaglandin synthesis accounts for the gastrointestinal toxicity of antiinflammatory drugs and that aspirin might prevent abortion and interfere with IUDs. Apparently, many actions of aspirin-like drugs are explained by a common mechanism. Aspirin's analgesic action is being investigated; an intermediate to prostaglandin release is the production of unstable cyclic peroxides; pain is now hypothesized to result from these fatty acid hydroperoxides, since pain was not caused by the parent fatty acids. Infusion of prostaglandins at high enough concentrations also caused hyperalgesia. Hence, 2 types of pain have been found capable of treatment by aspirin-like drugs--pain caused by synthesis of inflammatory substances (which aspirin blocks), and pain caused by sensitization of pain receptors.