Antinociceptive interaction between epidurally administered opioids and local anesthetics

我们评估了阿片类药物和局部麻醉剂对大鼠躯体和内脏刺激的抗伤害性相互作用。采用甩尾（TF）试验和结肠膨胀（CD）试验分别评估机体和内脏抗伤感受效应。大鼠被植入硬膜外导管，并接受布比卡因、芬太尼或两者联合的硬膜外注射。硬膜外给予布比卡因和芬太尼以剂量依赖性方式增加TF潜伏期和CD阈值。低剂量布比卡因与芬太尼联用，单独无抗痛觉作用，可使TE潜伏期延长，CD阈值升高。布比卡因和芬太尼联合使用不会加重运动麻痹。部分大鼠植入鞘内导管。吗啡、利多卡因或两者联合以1mu/h的恒定速率鞘内输注，持续6天。在TF和CD试验中，鞘内注射吗啡和利多卡因均产生剂量依赖性的抗感觉作用，在第1天达到峰值，第4天效果消失。小剂量吗啡与利多卡因联合输注对大鼠无明显镇痛作用。利多卡因可增强吗啡抗痛觉作用的持续时间和强度。等容积分析显示吗啡和利多卡因之间存在协同作用。这些结果证实了阿片类药物和局麻药的联合使用在临床上是有用的，可以增强抗痛觉作用，降低副作用的发生率和严重程度。

We evaluated the antinociceptive interaction between opioids and local anesthetics on both somatic and visceral stimuli in rats. Tail flick (TF) test and colorectal distention (CD) test were performed to estimate somatic and visceral antinociceptive effects, respectively. Rats were implanted epidural catheters and received an epidural injection of bupivacaine, fentanyl, or the combination of those. Epidurally administered bupivacaine and fentanyl increased TF latency and CD threshold in a dose-dependent fashion. The coadministration of low dose of bupivacaine and fentanyl, which had no antinociceptive effects alone, produced prolongation of TE latency and increased in CD threshold. The combination of bupivacaine and fentanyl did not potentiate motor paralysis.Some rats were implanted intrathecal catheters. Morphine, lidocaine, or the combination of those was infused intrathecally at a constant rate of 1mu/h for 6 days. Intrathecally infused morphine and lidocaine produced dose-dependent antinociceptive effects in both TF and CD tests with peak effects on day 1, and the effects disappeared on day 4. Coinfusion of low dose of morphine and lidocaine, which had no effects by themselves, produced significant antinociception. Coinfused lidocaine potentiated the duration and the magnitude of morphine antinociception. Isobolographic analysis showed a synergistic interaction between morphine and lidocaine.These results confirm that the combination of opioids and local anesthetics is clinically useful, potentiating the antinociceptive effects and reducing the incidence and severity of side effects.