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.
Botting
Regina
R
The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
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