Beilin B, Nemirovsky A Y, Zeidel A, Maibord E, Zelman V, Katz R L
Department of Anesthesiology, Rabin Medical Center, Golda Campus, Petach-Tikva, Israel.
Pain. 1997 Apr;70(2-3):217-21. doi: 10.1016/s0304-3959(97)03326-5.
In this study we evaluated the antinociceptive effect of concurrent intrathecal (i.t.) and subcutaneous (s.c.) administration of morphine and physostigmine, respectively. The experiments were performed on male Wistar rats. Intrathecal administration of morphine was performed through a catheter implanted in the subarachnoid space. The 'tail-immersion' test was used to measure animals' responses to evoked nociceptive stimuli. Interaction of drugs was analyzed using a dose addition model. Both i.t. (1-5 microg) administration of morphine and s.c. (50-250 microg/kg) administration of physostigmine increased the latencies of nociceptive responses in a dose-dependent manner. Two micrograms of i.t. morphine and 100 microg/kg of s.c. physostigmine demonstrated 31.6 +/- 10.6 and 34.2 +/- 11.4 percentage of maximal possible effect (%MPE), respectively. Simultaneous administration of 1 microg of i.t. morphine and 50 microg/kg of s.c. physostigmine produced a %MPE equal to 84.8 +/- 16.9. Thus, combined administration of 1 microg i.t. morphine and 50 microg/kg s.c. physostigmine resulted in a strong, highly significant antinociceptive effect. This effect was much higher than the effect expected if both drugs acted in an additive manner. Supra-additive interaction observed in this study might be a result of simultaneous activation of different neurotransmitter systems involved in nociceptive processing at the spinal as well as at the supraspinal level of the CNS.
在本研究中，我们分别评估了鞘内（i.t.）注射吗啡和皮下（s.c.）注射毒扁豆碱同时给药的抗伤害感受作用。实验在雄性Wistar大鼠身上进行。鞘内注射吗啡通过植入蛛网膜下腔的导管进行。采用“尾部浸入”试验来测量动物对诱发伤害性刺激的反应。使用剂量相加模型分析药物的相互作用。鞘内注射吗啡（1 - 5微克）和皮下注射毒扁豆碱（50 - 250微克/千克）均以剂量依赖性方式增加伤害性反应的潜伏期。2微克鞘内注射吗啡和100微克/千克皮下注射毒扁豆碱分别显示出最大可能效应的31.6±10.6%和34.2±11.4%。同时给予1微克鞘内注射吗啡和50微克/千克皮下注射毒扁豆碱产生的最大可能效应百分比为84.8±16.9。因此，联合给予1微克鞘内注射吗啡和50微克/千克皮下注射毒扁豆碱产生了强烈、高度显著的抗伤害感受作用。这种作用远高于两种药物以相加方式作用时预期的效果。本研究中观察到的超相加相互作用可能是由于在脊髓以及中枢神经系统的脊髓上水平参与伤害性处理的不同神经递质系统同时被激活所致。
