鞘内注射盐酸奈福泮和吗啡对切口痛大鼠脊髓c-fos表达的影响

Effects of intrathecal nefopam hydrochloride and morphine on spinal c-fos expression in a rat model of incisional pain

目的探讨在大鼠切口痛模型中鞘内注射奈福泮与吗啡在脊髓水平的抗伤害作用以及对脊髓c-fos表达的影响,并且测量二者相互作用时的半效剂量（ED50）。方法雄性SD大鼠85只,分为对照组、不同剂量奈福泮（50-150μg）组、不同剂量吗啡（3-10μg）组进行术前鞘内注射以获得量效曲线及ED50值;切口术前鞘内同时注射奈福泮和吗啡不同比例的ED50以观察联合用药时的ED50值。按Brennan法制成大鼠切口痛模型,采用累积疼痛评分法观察疼痛的行为学变化,以免疫组织化学法测量c-fos含量。结果与对照组比较,术前奈福泮、吗啡治疗组和奈福泮＋吗啡治疗组大鼠在术后1 h累积疼痛评分均明显降低（P〈0.05）;在Isobologram图中可见奈福泮与吗啡合用时的累积疼痛评分实测值明显落在理论累加等效线的下方,且95%可信区间不与理论累加点重合。与假手术组比较,对照组大鼠脊髓背角fos样免疫活性（FLI）阳性神经元表达明显升高（P〈0.01）;与对照组比较,术前奈福泮、吗啡治疗组和术前奈福泮＋吗啡治疗组脊髓背角FLI阳性神经元数目明显降低（P〈0.05）,1/2ED50量的两药联合用药的抑制百分比均比ED50量的两药单用的抑制百分比大（P〈0.05）。结论在大鼠切口疼痛模型中,术前鞘内注射奈福泮和吗啡能抑制脊髓内c-fos基因的表达,能产生量效相关的抗伤害作用,奈福泮与吗啡联合用药能产生协同作用。

Objective To observe the effect of antinociception and expression of c-fos in the spinal cord after the intrathecal administration of nefopam and morphine in a rat model of incisional pain,to survey the ED50 of two-way interaction.Methods Eighry-five male SD-rats were divided randomly into several groups.NS,nefopam（50～150 μg） and morphine（3～10 μg）were administered to obtain the dose-response curve and the ED50 values;fraction of ED50 values were administered intrathecally to establish the ED50 of drug combinations.According to the method of Breunan.Pain behavior was assessed at 1 h after incision by cumulative pain score.Immunohistochemistry was administered to survey the content of c-fos.Results In nefopam group,morphine group and nefopam plus morphine group,cumulative pain score was significantly lower than that in control group 1 h after incision.The real value of cumulative pain score in nefopam plus morphine group leave out the theoretical cumulative significantly on the isobologram and the 95% confidence interval was not coincident with theorial cumulative spot.The number of fos like immunoreactive of the spinal cord in control group were significantly more than those in the sham operation.In nefopam group,morphine group and nefopam plus morphine group,the number of FLI in the spinal cord was significantly less than those in control group（P〈0.05）.Inhibition-percentage in the 1/2ED50 both nefopam and morphine group was more than that in the ED50 of them alone（P〈0.05）.Conclusion In a rat model of incisional pain,intrathecal injection of nefopam and morphine could inhibit the expression of c-fos gene in spinal cord and create dose-response relative antinociceptic effect.Their combination could produce synergistic interaction.