The spinal actions of nonsteroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects

Drugs
K McCormack

Abstract

The traditional classification of nonsteroidal anti-inflammatory drugs (NSAIDs) as exclusively 'peripherally acting' agents is no longer valid. For many of these agents there is a growing body of evidence in favour of an additional central mechanism for their anti-inflammatory and analgesic effects. This view is further supported by the recent discovery that a substantial component of the hyperalgesia and allodynia that characterise postinjury hypersensitivity occurs in the CNS, notably the spinal dorsal horn. An important corollary is that inhibition of central nociceptive processing may represent an important analgesic mode of action for those NSAIDs that are effective in the management of pain after tissue injury. Historically, attempts to group this heterogeneous class of compounds into a single entity are largely derived from the observation that the majority of clinically useful NSAIDs are weak organic acids (pKa 3 to 5), bind extensively to plasma albumin (= 99%), and inhibit (to varying degrees) prostaglandin synthesis. However, the significance of these various unifying features is becoming increasingly obscure. While inhibition of prostaglandin synthesis apparently remains an important analgesic mode of action for NSA...Continue Reading

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