Kawamata T, Omote K, Kawamata M, Iwasaki H, Namiki A
Department of Anesthesiology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Anesthesiology. 1997 Aug;87(2):436-48. doi: 10.1097/00000542-199708000-00035.
The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.
Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.
Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.
The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.
鞘内注射α2肾上腺素能激动剂可乐定已被证明具有显著的抗伤害感受作用，尽管可乐定会导致低血压和心动过缓。鞘内注射可乐定与局部麻醉药联合使用可增强镇痛效果，然而这种联合用药可能会导致明显的低血压和运动阻滞，这可能会限制其临床应用。替扎尼定是另一种α2肾上腺素能激动剂，也能产生抗伤害感受作用，且不会引起明显的血流动力学变化。本研究旨在评估替扎尼定、可乐定与利多卡因之间的抗伤害感受及血流动力学相互作用。
雄性Sprague Dawley大鼠长期植入腰椎鞘内导管。采用甩尾试验评估热痛觉阈值。检测鞘内注射替扎尼定、可乐定、利多卡因或α2肾上腺素能激动剂与利多卡因联合用药改变甩尾潜伏期的能力。应用等效应线图分析法来描述抗伤害感受相互作用的特征。此外，还监测了鞘内注射药物及联合用药后的运动功能、血压和心率。
鞘内注射替扎尼定、可乐定或联合用药均能以剂量和时间依赖性方式增加甩尾潜伏期，且不影响运动功能。替扎尼定和可乐定的效价顺序（产生50%峰值效应的剂量，以微克计）分别为1.8和0.75。通过等效应线图分析，替扎尼定与利多卡因以及可乐定与利多卡因均显示出显著的协同抗伤害感受相互作用。效价比分析和分数分析也证实了这种协同相互作用。在联合用药产生相当抗伤害感受的剂量下，替扎尼定与利多卡因联合用药，与可乐定与利多卡因联合用药不同，不影响运动功能或血压。
作者的研究结果表明，鞘内注射替扎尼定和可乐定与利多卡因具有协同相互作用，从而增强了对躯体伤害性刺激的抗伤害感受程度。替扎尼定与利多卡因之间的抗伤害感受协同相互作用在临床实践中可能有用，且不影响血压、心率或运动功能。
