Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint.
A method has been developed to measure the analgesic action of aspirin-like drugs in knee joints of anaesthetized dogs. Bradykinin, injected into the joint cavity, induced a reflex rise in blood pressure which was dose-dependent; this was used as a measure of nociceptive activity. The joint cavity became more sensitive to bradykinin as the experiment proceeded, or when a low concentration of prostaglandin E1 or E2 was infused locally. The increase in sensitivity with time was prevented by local injection of aspirin or indomethacin, but that induced by exogenous prostaglandin infusion was not. Injections of carrageenin into dog knee joints increased the prostaglandin E2 content of synovial fluid by up to 160 ng per joint; indomethacin prevented this increase. These experiments support our previous conclusion that local biosynthesis of a prostaglandin (induced by mild trauma) sensitizes pain receptors to mechanical or chemical stimuli. Aspirin-like drugs are analgesic because they prevent prostaglandin biosynthesis, thereby preventing this sensitization.
D000698:Analgesia; D000818:Animals; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects
D011453:Prostaglandins; D011458:Prostaglandins E; D002351:Carrageenan; D008012:Lidocaine; D001241:Aspirin; D001920:Bradykinin; D007213:Indomethacin