NSAIDs action in the CNS

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to relieve pain by acting at the local site of injury, but they have also now been shown to relieve pain by CNS mechanisms. NSAIDs reduce inflammation and pain locally by inhibiting the enzyme cyclooxygenase-2 (COX-2), which inhibits formation of prostaglandin E2 (PGE2). PGE2 increases the sensitivity of peripheral nerves to pain. Scientists at Massachusetts General Hospital in Boston, however, now show that peripheral injury also induces COX-2 expression in the brain and spinal cord, and PGE2 increases the excitability of CNS neurons so that even nonpainful stimuli are perceived as painful, explaining why inflamed tissue feels sensitive and tender. Furthermore, inhibiting COX-2 in the CNS also decreases pain and hypersensitivity. The researchers suggest that targeting the widespread CNS production of COX-2 might more-effectively relieve pain as well as improve secondary symptoms such as lethargy, depression and loss of appetite. The study is in the March 22 issue of Nature.