Kaneko M, Saito Y, Kirihara Y, Collins J G, Kosaka Y
Department of Anesthesiology, Shimane Medical University, Izumo, Japan.
Anesthesiology. 1994 Jan;80(1):137-50. doi: 10.1097/00000542-199401000-00021.
Clinically, epidural coadministration of opioids and local anesthetics has provided excellent analgesia for various types of pain. However, information about the interaction of these drugs when administered epidurally is limited. Therefore, we evaluated the antinociceptive interaction between morphine and lidocaine on both somatic and visceral noxious stimuli in the rat.
Male Sprague-Dawley rats weighing 300-350 g had epidural catheters implanted at T13-L1. Every rat was tested with both the tail flick test, a somatic noxious stimulus, and the colorectal distension test, a visceral noxious stimulus. In the colorectal distension test, the response threshold was defined by the pressure within the intracolonic balloon required to trigger abdominal contraction. Tail flick latency and colorectal distension threshold were measured before and for 180 min after the administration of morphine, lidocaine, or combinations of those drugs. To characterize the interaction, isobolographic analysis was performed with a fixed morphine: lidocaine dose ratio of 1:1,000.
Epidural morphine (0.1-10 micrograms) and lidocaine (100-800 micrograms) increased the tail flick latency and colorectal distension threshold in a dose- and time-dependent fashion. The epidural injection of morphine (0.1-1 microgram) mixed with lidocaine (100 or 200 micrograms) significantly increased the peak effect and prolonged the duration of effects compared with each drug alone in both nociceptive tests. Areas under the curves, calculated to express overall magnitude and duration of antinociceptive effects, were significantly increased by combinations as compared with each drug alone, especially with morphine 0.1 microgram and lidocaine 100 or 200 micrograms, each of which alone produced no change in the area under the curve. Isobolographic analysis revealed that epidural morphine and lidocaine interact synergistically at 10, 20, and 30 min after injection in both somatic and visceral nociception tests. Both potency ratio analysis and fractional analysis confirmed the finding of the isobolographic analysis. Epidural naloxone antagonized the antinociceptive effects produced by the combination.
These data demonstrate that epidurally coadministered morphine and lidocaine produce synergistic analgesia and prolong the duration of analgesia in tests of somatic and of visceral nociception.
临床上，硬膜外联合使用阿片类药物和局部麻醉药已为各类疼痛提供了良好的镇痛效果。然而，关于这些药物硬膜外给药时相互作用的信息有限。因此，我们评估了吗啡和利多卡因对大鼠躯体和内脏伤害性刺激的抗伤害感受相互作用。
体重300 - 350克的雄性Sprague-Dawley大鼠在T13 - L1植入硬膜外导管。每只大鼠均接受甩尾试验（一种躯体伤害性刺激）和结直肠扩张试验（一种内脏伤害性刺激）测试。在结直肠扩张试验中，反应阈值由触发腹部收缩所需的结肠内球囊压力确定。在给予吗啡、利多卡因或这些药物的组合之前及之后180分钟测量甩尾潜伏期和结直肠扩张阈值。为了表征相互作用，以固定的吗啡：利多卡因剂量比1:1000进行等效线图分析。
硬膜外注射吗啡（0.1 - 10微克）和利多卡因（100 - 800微克）以剂量和时间依赖性方式增加甩尾潜伏期和结直肠扩张阈值。在两种伤害感受测试中，与单独使用每种药物相比，硬膜外注射吗啡（0.1 - 1微克）与利多卡因（100或200微克）混合显著增加了峰值效应并延长了效应持续时间。计算得出的曲线下面积用于表示抗伤害感受作用的总体大小和持续时间，与单独使用每种药物相比，联合用药时曲线下面积显著增加，尤其是吗啡0.1微克与利多卡因100或200微克联合使用时，单独使用这两种药物时曲线下面积均无变化。等效线图分析显示，在躯体和内脏伤害感受测试中，硬膜外注射吗啡和利多卡因在注射后10、20和30分钟时产生协同作用。效价比分析和分数分析均证实了等效线图分析的结果。硬膜外注射纳洛酮可拮抗联合用药产生的抗伤害感受作用。
这些数据表明，在躯体和内脏伤害感受测试中，硬膜外联合使用吗啡和利多卡因可产生协同镇痛作用并延长镇痛持续时间。
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