Antinociceptive interaction between epidurally administered opioids and local anesthetics

我们评估了阿片类药物和局麻药对大鼠躯体和内脏刺激的抗伤害性相互作用。采用甩尾（TF）试验和结直肠扩张（CD）试验分别评价躯体和内脏的镇痛作用。大鼠被植入硬膜外导管，并接受硬膜外注射布比卡因，芬太尼，或这些组合。硬膜外给药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。小剂量布比卡因与芬太尼合用时，TE潜伏期延长，CD阈值增加，而芬太尼单独使用时无镇痛作用。布比卡因和芬太尼的组合并不增强运动麻痹。一些大鼠被植入鞘内导管。吗啡、利多卡因或两者联合以1mu/h的恒速鞘内注射6天。鞘内注入吗啡和利多卡因产生剂量依赖性的抗伤害效应在TF和CD测试与峰值效应在第1天，和效果消失的第4天。低剂量吗啡和利多卡因单独给药无明显镇痛作用，但两者合用时有明显的镇痛作用。利多卡因可增强吗啡镇痛作用的持续时间和强度。等辐射分析表明吗啡和利多卡因之间存在协同作用，这些结果证实阿片类药物和局麻药的组合在临床上是有用的，增强了抗伤害效应，降低了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.