Managing Pain

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Science  25 Oct 2002:
Vol. 298, Issue 5594, pp. 705
DOI: 10.1126/science.298.5594.705a

The current arsenal of drugs to quell acute pain, fever, and inflammation includes nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (Cox) enzymes. Most traditional NSAIDs do not distinguish between the two known Cox isoforms, Cox-1 and −2, but the newer generation of coxibs are selective and are used clinically for the management of pain symptoms. However, neither isozyme is sensitive to therapeutic concentrations of acetaminophen, one of the most popular analgesic and antipyretic drugs used worldwide. It has been postulated that acetaminophen could act on a brain-specific Cox.

Chandrasekharan et al. have now identified Cox-3, a third distinct enzyme that derives from the same gene as Cox-1 but retains a single intron because of an unusual form of alternative splicing. Cox-3 is highly expressed in the human cerebral cortex and in heart tissue. Its activity appears to be different pharmacologically from that of Cox-1 and −2 and shows greater sensitivity to various analgesic and antipyretic drugs and NSAIDs, including acetaminophen, aspirin, and ibuprofen. Thus Cox-3 may represent the long-sought-after target of acetaminophen in the central nervous system. — LC

Proc. Natl. Acad. Sci. U.S.A 10.1073/pnas.162468699 (2002).

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