COX-1 and COX-3 inhibitors.
Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory action of aspirin requires a much higher dose. It is possible that inhibition of cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic and antipyretic effects, and inhibition of COX-2 is responsible for its anti-inflammatory action. We compared the analgesic effects of an aspirin-like drug (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse stretching test and confirmed that the analgesic action of the aspirin-like drug was peripheral. Two possible sites have been postulated for the antipyretic action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in endothelial cells of hypothalamic blood vessels or (b) inhibition of COX synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal afferents. The antipyretic action of aspirin may be mediated by inhibition of COX-3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to sensory receptors of peripheral vagal afferents. It is also possible that both enzymes are involved in the antipyretic action of aspirin. Whereas lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice, suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection.
The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
Regina
R
Botting
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000188:drug therapy / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C466421:cyclooxygenase-3; D001241:Aspirin