Penning J P, Yaksh T L
Department of Anesthesiology, Ottawa Civic Hospital, Ontario, Canada.
Anesthesiology. 1992 Dec;77(6):1186-2000. doi: 10.1097/00000542-199212000-00021.
The interaction in the rat between intrathecal morphine and local anesthetics (bupivacaine and lidocaine) on nociception (52.5 degrees C hot plate and paw pressure), motor function, and autonomic function (blood pressure [BP] and heart rate [HR]) was examined over a range of doses for both morphine and the local anesthetics. High doses of intrathecal bupivacaine (75 micrograms) or lidocaine (500 micrograms) produced motor block and hypotension (150 micrograms bupivacaine) lasting approximately 15 and 7 min, respectively, whereas low doses of intrathecal bupivacaine (25 micrograms) and lidocaine (100 micrograms) produced only a transient motor weakness lasting 2 min or less. Alone, neither agent altered the hot plate or paw pressure response at doses, or at times, where the agents had no effect upon motor function. In contrast, at the low dose of either local anesthetic, after the resolution of the transient motor weakness, these doses resulted in a significant leftward shift in the dose-response curves for intrathecal morphine on both the hot plate and paw pressure, as measured by the maximum observed peak effect and by the area under the time-effect curve. Thus, for example, the morphine ED50 (95% confidence intervals) for morphine/saline was 1.7 micrograms (0.7-1.9) on the hot plate and 1.1 micrograms (0.8-1.4) on the paw pressure versus for morphine/bupivacaine (25 micrograms): hot plate 0.25 micrograms (0.21-0.42) and paw pressure 0.28 micrograms (0.2-0.4). Intrathecal morphine was not observed to have any effect on the dose-dependent effects of intrathecal bupivacaine on motor or autonomic blockade. Comparable results were also observed with lidocaine (bupivacaine was found to have no significant effect on spinal cord morphine clearance). We conclude that low doses of intrathecal lidocaine and bupivacaine, which alone have no antinociceptive effect, at times when motor function was clearly unimpaired, are able to significantly augment the antinociceptive activity of intrathecal morphine on the hot plate and paw pressure tests. This prominent and selective potentiation appears to occur via a non-pharmacokinetic mechanism and probably reflects upon the interaction of low concentrations of local anesthetics with systems in the spinal dorsal horn that process acute high threshold afferent input.
研究了鞘内注射吗啡与局部麻醉药（布比卡因和利多卡因）在大鼠体内对伤害感受（52.5℃热板法和 paw 压力法）、运动功能及自主神经功能（血压[BP]和心率[HR]）的相互作用，涉及吗啡和局部麻醉药的一系列剂量。高剂量鞘内注射布比卡因（75 微克）或利多卡因（500 微克）可产生运动阻滞和低血压（150 微克布比卡因），持续时间分别约为 15 分钟和 7 分钟，而低剂量鞘内注射布比卡因（25 微克）和利多卡因（100 微克）仅产生持续 2 分钟或更短时间的短暂运动无力。单独使用时，在这些药物对运动功能无影响的剂量或时间下，两种药物均未改变热板法或 paw 压力法反应。相反，在两种局部麻醉药的低剂量下，短暂运动无力消退后，这些剂量导致鞘内注射吗啡在热板法和 paw 压力法上的剂量-反应曲线显著左移，通过最大观察到的峰值效应和时效曲线下面积来衡量。因此，例如，吗啡/生理盐水组在热板法上吗啡的 ED50（95%置信区间）为 1.7 微克（0.7 - 1.9），在 paw 压力法上为 1.1 微克（0.8 - 1.4），而吗啡/布比卡因（25 微克）组：热板法为 0.25 微克（0.21 - 0.42），paw 压力法为 0.28 微克（0.2 - 0.4）。未观察到鞘内注射吗啡对鞘内注射布比卡因在运动或自主神经阻滞方面的剂量依赖性效应有任何影响。利多卡因也观察到了类似结果（发现布比卡因对脊髓吗啡清除率无显著影响）。我们得出结论，低剂量鞘内注射利多卡因和布比卡因，单独使用时无抗伤害感受作用，在运动功能明显未受损害时，能够显著增强鞘内注射吗啡在热板法和 paw 压力法测试中的抗伤害感受活性。这种显著且选择性的增强作用似乎通过非药代动力学机制发生，可能反映了低浓度局部麻醉药与脊髓背角中处理急性高阈值传入输入的系统之间的相互作用。
