Perrot S, Kayser V, Fournié-Zaluski M C, Roques B P, Guilbaud G
I.N.S.E.R.M. U 161, Paris, France.
Eur J Pharmacol. 1993 Sep 7;241(1):129-33. doi: 10.1016/0014-2999(93)90944-d.
The antinociceptive effects of various i.v. doses (2.5, 3.75, 5, 10, 15 and 20 mg/kg) of a prodrug mixed inhibitor of enkephalin degrading enzymes, PC 12, were tested in normal and Freund's adjuvant-induced arthritic rats, using vocalization thresholds to paw pressure as a nociceptive test. In normal animals, PC 12 produced a dose-dependent antinociceptive effect over the 2.5-15 mg/kg range, but the time-course of the response was shorter with the dose of 20 mg/kg. In arthritic rats, PC 12 had no significant effect at 2.5 mg/kg, but induced a highly significant dose-dependent antinociceptive action with 3.5 and 5 mg/kg, which decreased with the highest doses. The antinociceptive effect of PC 12 (10 mg/kg i.v.) was prevented by naloxone (0.5 mg/kg i.v.) in the two categories of rats, providing evidence for the involvement of opioid receptors. These results are discussed in relation with the increased level of endogenous opioid substances in the spinal dorsal horn of arthritic rats and the nociceptive test used.
采用爪部压力发声阈值作为痛觉测试，在正常大鼠和弗氏完全佐剂诱导的关节炎大鼠中，测试了不同静脉注射剂量（2.5、3.75、5、10、15和20mg/kg）的脑啡肽降解酶前体药物混合抑制剂PC 12的抗伤害感受作用。在正常动物中，PC 12在2.5 - 15mg/kg范围内产生剂量依赖性抗伤害感受作用，但20mg/kg剂量时反应的时间进程较短。在关节炎大鼠中，PC 12在2.5mg/kg时无显著作用，但在3.5和5mg/kg时诱导出高度显著的剂量依赖性抗伤害感受作用，而在最高剂量时这种作用减弱。在两类大鼠中，纳洛酮（0.5mg/kg静脉注射）可阻断PC 12（10mg/kg静脉注射）的抗伤害感受作用，这为阿片受体的参与提供了证据。结合关节炎大鼠脊髓背角内源性阿片物质水平的升高以及所采用的痛觉测试对这些结果进行了讨论。
