Tissue damage results in the release of inflammatory mediators, including prostaglandins, which sensitise fine nerve endings in the periphery to mechanical and thermal changes. Sensitisation of these nerve endings, or nociceptors, contributes to the phenomenon of hyperalgesia, which routinely accompanies tissue damage. It has been shown that the acidic antipyretic analgesics reduce or down-regulate the enhanced nociceptor sensitivity in damaged tissue, an effect probably attributable to inhibition of prostaglandin synthesis.
Recent studies suggest that these drugs may have an additional mechanism of action in the spinal cord or higher centres. When enantiomers of flurbiprofen were used in the rat, it was shown that S- and R-flurbiprofen exert differential antinociceptive effects. The R-enantiomer, which is practically devoid of peripheral cyclo-oxygenase inhibitory activity in vitro, showed comparable analgesic potency to the S-enantiomer, which does inhibit cyclo-oxygenase activity, in experimental models of nociception. It is possible that the antinociceptive action of the R-enantiomer is related to a reduction in prostaglandin synthesis in the CNS rather than at the site of tissue damage, although other mechanisms may also contribute to its antinociceptive action.
In contrast to earlier indications, it would appear that a significant part of the antinociceptive action of the antipyretic analgesics is exerted in the spinal cord. The observed accumulation of acidic antipyretic analgesics in inflamed tissue may account for the superior anti-inflammatory activity of these latter compounds.