Antinociceptive interaction between epidurally administered opioids and local anesthetics

硬膜外阿片类药物和局部麻醉药之间的抗伤害相互作用

• 批准号: 08671735
• 负责人: KOSAKA Yoshihiro
• 金额: $ 1.34万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671735/
• 关键词: opioid; local anesthetics; epidural; somatic pain; visceral pain; フェンタニール; ブピバカイン

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.

我们评价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)实验和大肠扩张(CD)实验分别评价躯体和内脏的抗伤害效应。大鼠被植入硬膜外导管，并接受硬膜外注射布比卡因、芬太尼或它们的组合。硬膜外注射布比卡因和芬太尼以剂量依赖的方式增加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阈值升高。布比卡因和芬太尼的联合应用并没有加强运动瘫痪。一些大鼠被植入鞘内导管。鞘内注入吗啡、利多卡因或两者的组合，以1亩/小时的恒定速度持续6天。鞘内注射吗啡和利多卡因均可产生剂量依赖性的抗伤害效应，在第1天达到高峰，第4天消失。小剂量吗啡和利多卡因联合应用均无明显的抗伤害效应。混合注入的利多卡因增强了吗啡抗伤害作用的持续时间和强度。等位图分析显示吗啡与利多卡因之间存在协同作用，证实阿片类药物与局麻药联合应用具有临床应用价值，可增强抗伤害性作用，降低副作用的发生率和严重程度。

项目成果

Yoji Saito: "Interaction of intrathecally infused morphine and lidocaine in rats (Part I) Synergistic antinociceptive effects" Anesthesiology. Vol.89-No.6. 1455-1463 (1998)

Yoji Saito：“大鼠鞘内注射吗啡和利多卡因的相互作用（第一部分）协同镇痛作用”麻醉学。

Yoji Saito: "Interaction of intrathecally infused morphine and lidocaine in rats (part I) : Snergiatic antinociceptive effects" Anesthesiology. 89・6. 1455-1463 (1998)

Yoji Saito：“大鼠鞘内注射吗啡和利多卡因的相互作用（第一部分）：Snergiatic 镇痛作用”麻醉学 89・6（1998）。