Pelissier Teresa, Laurido Claudio, Kramer Verónica, Hernández Alejandro, Paeile Carlos
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70,000, Santiago 7, Chile.
Eur J Pharmacol. 2003 Sep 5;477(1):23-8. doi: 10.1016/s0014-2999(03)02192-7.
To study the antinociceptive synergy resulting from the combination of opioid receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists on neuropathic pain, an isobolographic analysis of equianalgesic combinations of ketamine with methadone or morphine was performed in rats with mononeuropathy produced by placing four constrictive ligatures around the common sciatic nerve. Two weeks later, the antinociceptive effect of subcutaneous administration of the drugs alone or combined was evaluated by using the paw pressure test. Drugs and their combinations produced dose-dependent antinociception. Combinations produced synergy of a supra-additive nature in the neuropathic paw, but only additive antinociception in the normal paw. The ketamine/methadone combination was more effective to produce antinociception in the neuropathic paw than was the ketamine/morphine association, as revealed by the lower ED25. The results indicate supra-additive synergy between NMDA receptor antagonists and opioids, especially methadone, to produce antinociception in experimental neuropathy.
为研究阿片受体激动剂与N-甲基-D-天冬氨酸（NMDA）受体拮抗剂联合使用对神经性疼痛产生的镇痛协同作用，在通过对坐骨神经周围进行四处缩窄结扎制作单神经病的大鼠中，对氯胺酮与美沙酮或吗啡的等效镇痛组合进行了等效应线分析。两周后，通过爪部压力试验评估单独给药或联合给药的皮下给药镇痛效果。药物及其组合产生剂量依赖性镇痛作用。组合在神经性爪部产生超相加性质的协同作用，但在正常爪部仅产生相加性镇痛作用。如较低的半数有效剂量（ED25）所示，氯胺酮/美沙酮组合在神经性爪部产生镇痛作用比氯胺酮/吗啡组合更有效。结果表明，NMDA受体拮抗剂与阿片类药物，尤其是美沙酮之间存在超相加协同作用，可在实验性神经病变中产生镇痛作用。
