Central analgesic activity of nonsteroidal antiinflammatory drugs in animal and human pain models.

Nonsteroidal antiinflammatory drugs (NSAIDs) often are considered peripherally acting analgesics. This traditional view has been challenged by several authors who have put forward evidence for a central analgesic action for both acidic and nonacidic NSAIDs. The most compelling evidence, reviewed in this report, comes from well-defined animal pain models in which central administration of low doses of NSAIDs provides effective analgesia. In humans, the nociceptive flexion reflex provides a valuable means of dissociating central and peripheral effects. The mechanism of the central action of NSAIDs remains unclear. Several lines of evidence implicate the inhibition of central prostaglandin synthesis, particularly in models with a strong hyperalgesic component to their pathophysiology. However, not all potent inhibitors of prostaglandin synthesis are active by central routes of administration, and it seems likely that other actions may be involved.