Goodchild C S, Sanghera S, Serrao J M, Gent J P
Department of Anaesthesia, University of Leeds, United Kingdom.
Eur J Anaesthesiol. 1991 May;8(3):227-31.
The results from 44 experiments performed on 13 rats with chronically implanted lumbar subarachnoid catheters are reported. ICI 197 067 produced dose-dependent segmental analgesic effects when measurement of electrical current threshold for pain was used as the nociceptive test. Ten microliters of intrathecal ICI 197 067 (0.06 mg ml-1; 1.5 nmol) caused a significant rise in the current threshold for pain in the tail of 1.56 +/- 0.04 x control (mean +/- SEM) but no significant change in pain threshold in the neck (1.03 +/- 0.03 x control). By contrast, simultaneous measurements of tail-flick latency in these animals revealed no significant rise in pain thresholds using this nociceptive test. Intraperitoneally administered naloxone produced a dose-dependent suppression of the spinally mediated analgesic effect produced by ICI 197 067; the ED50 for this effect was 0.79 mumol kg-1, a value very close to the ED50 for naloxone antagonism of ketocyclazocine spinally mediated analgesia. We conclude that ICI 197 067 produces spinally mediated analgesia by binding to spinal-cord kappa-opioid receptors.
报告了对13只长期植入腰蛛网膜下腔导管的大鼠进行的44项实验结果。当将疼痛电流阈值测量用作伤害性测试时，ICI 197 067产生剂量依赖性节段性镇痛作用。鞘内注射10微升ICI 197 067（0.06毫克/毫升；1.5纳摩尔）导致尾部疼痛电流阈值显著升高至对照的1.56±0.04倍（平均值±标准误），但颈部疼痛阈值无显著变化（1.03±0.03倍对照）。相比之下，在这些动物中同时测量甩尾潜伏期发现，使用该伤害性测试时疼痛阈值无显著升高。腹腔注射纳洛酮对ICI 197 067产生的脊髓介导镇痛作用产生剂量依赖性抑制；该作用的半数有效剂量（ED50）为0.79微摩尔/千克，这一数值与纳洛酮拮抗酮环唑新脊髓介导镇痛作用的ED50非常接近。我们得出结论，ICI 197 067通过与脊髓κ-阿片受体结合产生脊髓介导的镇痛作用。
