Weak inhibitors of cyclooxygenases may exert their antinociceptive effect by modulation of transcription factors.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain, fever and inflammation. For these agents inhibition of prostaglandin synthesis via inhibition of cyclooxygenases (COX) is considered to be their principle mode of action.1 However, inhibition of prostaglandin synthesis alone may not account for all effects of NSAIDs. There is no satisfying correlation between inhibition of prostaglandin synthesis and antinociceptive (analgesic) effects of some of these agents.2 Weak inhibitors of prostaglandin synthesis, e. g. salicylic acid exert potent antinociceptive effects.3 Such observations question the conventual concept that NSAIDs act exclusively by inhibiting prostaglandin synthesis. However, neither the cellular target nor cell signaling pathways possibly involved in the antinociceptive effect of weak prostaglandin inhibitors have been identified yet.