Kayser V, Besson J M, Guilbaud G
Unité de Recherche de Physiopharmacologie du Système Nerveux, I.N.S.E.R.M., U 161, Paris, France.
Eur J Pharmacol. 1991 Mar 19;195(1):37-45. doi: 10.1016/0014-2999(91)90379-5.
The effects of the analgesic agent tramadol (0.1-1 mg/kg i.v.) were compared to those of the mixed agonist-antagonist analgesics nalbuphine (1 mg/kg i.v.) and buprenorphine (3 micrograms/kg i.v.) in the vocalization threshold to paw pressure test. Normal and Freund's adjuvant-induced arthritic rats were used. We have shown previously that these animals used as a model of clinical pain exhibit an enhanced sensitivity to morphine (0.1-1 mg/kg i.v.), with a rapid development of tolerance after repetitive low doses, a response not observed in normal rats. In the present study, the antinociceptive effects of tramadol, buprenorphine and nalbuphine were enhanced (by 2- to 5-fold) in arthritic compared to normal rats. In this model, these effects were significantly reduced by a dose of naloxone (0.1 mg/kg i.v.) that completely antagonized the effect of morphine. In this model, the antinociceptive effect of tramadol (1 mg/kg i.v.) was comparable to that of nalbuphine (1 mg/kg i.v.), buprenorphine (3 micrograms/kg i.v.) and morphine (1 mg/kg i.v.). Repeated administration of low doses of tramadol twice daily for 4 days to arthritic rats did not induce tolerance, in contrast to nalbuphine, buprenorphine, and morphine. In addition, no cross-tolerance between tramadol and morphine was observed in these animals.
在爪部压力发声阈值测试中，将镇痛剂曲马多（静脉注射0.1 - 1毫克/千克）的效果与混合激动剂-拮抗剂镇痛药纳布啡（静脉注射1毫克/千克）和丁丙诺啡（静脉注射3微克/千克）的效果进行了比较。使用了正常大鼠和弗氏佐剂诱导的关节炎大鼠。我们之前已经表明，这些用作临床疼痛模型的动物对吗啡（静脉注射0.1 - 1毫克/千克）表现出增强的敏感性，在重复低剂量给药后会迅速产生耐受性，而正常大鼠中未观察到这种反应。在本研究中，与正常大鼠相比，曲马多、丁丙诺啡和纳布啡在关节炎大鼠中的抗伤害感受作用增强了（2至5倍）。在这个模型中，一剂纳洛酮（静脉注射0.1毫克/千克）显著降低了这些作用，该剂量完全拮抗了吗啡的作用。在这个模型中，曲马多（静脉注射1毫克/千克）的抗伤害感受作用与纳布啡（静脉注射1毫克/千克）、丁丙诺啡（静脉注射3微克/千克）和吗啡（静脉注射1毫克/千克）相当。与纳布啡、丁丙诺啡和吗啡不同，对关节炎大鼠每天两次重复给予低剂量曲马多，持续4天，并未诱导出耐受性。此外，在这些动物中未观察到曲马多和吗啡之间的交叉耐受性。
