鞘内联合应用奈福泮和新斯的明对切口痛大鼠的镇痛效应

Effects of intrathecal nefopam and neostigmine on incision pain in rats

目的观察鞘内联合应用盐酸奈福泮和新斯的明的镇痛作用。方法在大鼠切口疼痛模型上结合鞘内置管技术,采用累积疼痛评分法评定大鼠疼痛行为;采用序贯法分别使用不同剂量奈福泮、新斯的明进行鞘内注射以获得量效曲线及半效剂量(ED50),鞘内联合应用不同比例的ED50剂量获得联合用药时药物各自的半效剂量以分析两药的相互作用。结果①据公式得出鞘内注射50-150μg的奈福泮的ED50值为82.64μg,95%可信区间为80.4-97.4μg;鞘内注射剂量1-10μg的新斯的明的ED50值为8.36μg,95%可信区间为6.68-10.70μg;鞘内合用1/2,1/4,1/8,1/16 ED50的奈福泮和新斯的明各自的ED50值分别为:奈福泮10.93μg,95%可信区间6.83-17.49μg;新斯的明1.05μg,95%可信区间为0.66-1.68μg。②奈福泮和新斯的明单独应用及联合应用对切口疼痛大鼠均产生剂量依赖型的镇痛作用。③据Tallarida等提出的Isobologram作图方法分析得出新斯的明和奈福泮的相互作用是协同的。结论①奈福泮50-150μg、新斯的明5-15μg鞘内应用均可产生剂量依赖性的镇痛作用。②奈福泮和新斯的明的镇痛作用存在协同作用。

Objective To explore the effect of intrathecal nefopam and neostigmine on postoperative pain in rats.Methods After intrathecal implantation,the incision pain rat models were established and used to evaluate the pain behaviors by cumulative pain scores.The dose-response curve and the 50% effective dose（ED50）were obtained after intrathecal injection of neostigmine and nefopam using sequential methods.The ED50 of neostigmine and nefopam were calculated for observing the drug interactions when different fractions of ED50 of both neostigmine and nefopam were administered together.Results ①The ED50 of intrathecal nefopam（50-150 μg） alone was 82.64 μg and 95% confidence intervals（CI）were 72.53-94.14 μg.The ED50 of intrathecal neostigmine（1-10 μg）alone was 8.36 μg and 95% confidence intervals were 6.68-10.70 μg.When the two drugs were used together at the doses of 1/2ED50,1/4ED50,1/8ED50 and 1/16ED50,the ED50 of nefopam was 10.93 μg（95%CI 6.83-17.49 μg）,and the ED50 of neostigmine was 1.05 μg（95%CI 0.66-1.68 μg）.②Intrathecal administration of nefopam,neostigmine or their combination produced a significant dose-dependent analgesic effect in incision pain rats.③According to the Isobologram methods by Tallarida,it was deduced that nefopam and neostigmine had the synergistic analgesic interaction.Conclusion ①Nefopam at the dose of 50-150 μg and neostigmine at the dose of 1-10 μg,both can produce a dose-dependant analgesic effect.②The analgesic effect of neotigmine and nefopam was synergistic.