鞘内注射盐酸奈福泮和吗啡的相互作用

INTERACTION OF INTRATHECAL NEFOPAM HYDROCHLORIDE AND MORPHINE

目的:研究鞘内注射盐酸奈福泮和吗啡在大鼠切口痛抗伤害作用时的半效有效剂量(ED50)及对脊髓背角c-Fos表达的影响,以探讨两者联合用药时的相互作用及镇痛机制。方法:用序贯法求出奈福泮与吗啡单独使用时ED50,再分别求两药ED50的1/2,1/4,1/8,1/16合用时各自的ED50。用两药合用时的ED50与单独使用时的ED50作等效曲线及免疫组化测量1/2 ED50剂量时奈福泮和/或吗啡对FLI-N产生的抑制率来分析两者的相互作用。结果:(1)奈福泮对切口镇痛作用的ED50值为88.5μg,吗啡的ED50为5.30μg;两者联合用药时奈福泮的ED50值为10μg,吗啡的ED50为0.60μg。(2)在Isobologram图见奈福泮与吗啡合用时的ED50实测值落在理论值的下方,两点作t检验的P<0.05。(3)1/2ED50量的两药联合对脊髓背角FLI-N抑制率均比单用药的抑制率大(P<0.05)。结论:鞘内注射奈福泮和吗啡的抗伤害作用与脊髓内c-Fos基因的表达有关,两药在等效剂量附近表现出协同效应。

Objective： To observe the ED50 and effct of spinal c-Fos expression after intrathecal nefopam and morphine in a rat model of incisional pain,and investigate whether the interaction of them are syne-rgistic mechnism.Methods： Sequential procedure abstain the ED50 of nefopam and morphine alone re-spectively,combinational injection 1/2,1/4,1/8,1/16 of their ED50 could get the respectively ED50 of com-bination,Then making Isobologram with ED50 of the combination and ED50 of each drugs,and surveying inhibition ratio of FLI-N in the ED50 of nefopam and morphine groups by immunohisto-chemistry in orde to study their interaction.Results：（1） ED50 of intrathecal nefopam and morphine after pain were,respectiv-ely,88.5μg and 5.30μg.The combinational ED50 were 10μg for nefopam and 0.60μg for morphine.（2） The realistie value in nefopam morphine groups leaved out the theorial value on the Isobologram,the two spot make t-test significantly.（3） The inhibition percentage of spinal FLI-N（Fos like immunoreactive-nervse） in the 1/2 ED50 of nefopam-morphine group was more significatively in the ED50 of them alone（P 0.05）.Conclusion： antinociceptic effect of intrathecal nefopam and morphine could do expression of c-Fos gene in spinal cord relativly.equivalent dose of them produce synergistic interaction.