CORRELATION BETWEEN NONSTEROIDAL ANTIINFLAMMATORY DRUG EFFICACY IN A CLINICAL PAIN MODEL AND THE DISSOCIATION OF THEIR ANTIINFLAMMATORY AND ANALGESIC PROPERTIES IN ANIMAL-MODELS

Recently our group demonstrated that it is possible to differentiate nonsteroidal anti-inflammatory drugs (NSAIDs) as analgesic agents in the management of acute musculoskeletal pain. In this paper, we extend this work to investigate the notion that the analgesic and anti-inflammatory potency of an NSAID is not simply related through a common mechanism, namely the inhibition of peripheral prostaglandin (PG) synthesis. Following an extensive survey of the published literature for a series of acidic NSAIDs, we could not find any significant correlation between potency as an analgesic agent or as an anti-inflammatory agent and analgesic efficacy in clinical practice. Importantly, we now demonstrate for the first time that it is potency as an analgesic agent relative to potency as an anti-inflammatory agent that covaries with clinical efficacy. We discuss the possibility that, for a given NSAID, the magnitude of this dissociation between analgesic and anti-inflammatory potencies may reflect the net effect of a complex interaction between peripheral and central sites of action, and between diverse mechanisms of action that are independent of an inhibition of PG synthesis. Our results provide a clinically meaningful differentiation of NSAIDs through the use of in vivo data.