COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites - PubMed (original) (raw)

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COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites

Maria Burian et al. Pharmacol Ther. 2005 Aug.

Abstract

Despite the diverse chemical structure of aspirin-like drugs, the antinociceptive effect of NSAIDs is mainly due to their common property of inhibiting cyclooxygenases involved in the formation of prostaglandins. Prostaglandins are potent hyperalgesic mediators which modulate multiple sites along the nociceptive pathway and enhance both transduction (peripheral sensitizing effect) and transmission (central sensitizing effect) of nociceptive information. Inhibition of the formation of prostaglandins at peripheral and central sites by NSAIDs thus leads to the normalisation of the increased pain threshold associated with inflammation. The contribution of peripheral and central mechanisms to the overall antinociceptive action of NSAIDs depends on several factors including the location of the targets of drug action, the site of drug delivery and the uptake and distribution to the site of action. The present work reviews the data on the regulation and location of cyclooxygenases at central and peripheral sites of the nociceptive pathway and focuses on the role of COX in the generation and maintenance of pain hypersensitivity. Experimental and clinical evidences are used to evaluate the significance of the peripheral and central antihyperalgesic effects of NSAIDs.

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