Central Components of the Analgesic/ Antihyperalgesic Effect of Nimesulide: Studies in Animal Models of Pain and Hyperalgesia

The analgesic action of NSAIDs has been attributed to the peripheral inhibition of prostaglandin synthesis via the blockade of the enzyme cyclo-oxygenase (COX) and prevention of bradykinin and cytokine-induced hyperalgesia via inhibition of the release of tumour necrosis factor-α. However, it is becoming increasingly evident that NSAIDs exert their analgesic effect through several mechanisms. Recent data suggest that significant expression of COX-2 is found in the central nervous system, where COX-2 seems to have, together with nitric oxide, an important role in spinal nociceptive transmission. Nitroglycerin is a nitric oxide donor and induces a hyperalgesic state, partially mediated by central mechanisms. Nimesulide is a preferential COX-2 inhibitor widely used to treat pain.