Moncada S, Ferreira S H, Vane J R
Eur J Pharmacol. 1975 Apr;31(2):250-60. doi: 10.1016/0014-2999(75)90047-3.
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.
已开发出一种方法来测量阿司匹林类药物在麻醉犬膝关节中的镇痛作用。将缓激肽注入关节腔会引起血压反射性升高，且呈剂量依赖性；这被用作伤害性活动的一种度量。随着实验进行，或者当局部注入低浓度的前列腺素E1或E2时，关节腔对缓激肽变得更加敏感。阿司匹林或吲哚美辛局部注射可防止敏感性随时间增加，但外源性前列腺素注入所诱导的敏感性增加则不受影响。向犬膝关节注射角叉菜胶可使关节滑液中前列腺素E2含量增加多达每关节160纳克；吲哚美辛可防止这种增加。这些实验支持了我们之前的结论，即（由轻度创伤诱导的）前列腺素的局部生物合成会使疼痛感受器对机械或化学刺激敏感。阿司匹林类药物具有镇痛作用，因为它们可防止前列腺素生物合成，从而防止这种敏感化。
