右美托咪定及舒芬太尼联合鞘内注射对CCI模型大鼠的镇痛效应

ANALGESIC EFFECTS OF DEXMEDETOMIDINE COMBINED WITH SUFENTANIL INTRATHECALLY INJECTION ON CCI MODEL IN RATS

目的：研究右美托咪定及舒芬太尼联合鞘内注射对CCI模型大鼠的镇痛效应。方法：鞘内置管成功的雄性SD大鼠50只,随机分成5组：假手术组（Sham组）;模型对照组（CCI组）;右美托咪定组（Dex组）;舒芬太尼组（Suf组）;右美托咪定＋舒芬太尼组（DS组）。Dex组、Suf组、DS组分别于术后1～14 d每天鞘内注射右美托咪定（dexmedetomidine,Dex）2μg/（kg.d）、舒芬太尼（sufentanil,Suf）1μg/d、Dex 1μg/（kg.d）＋Suf 0.5μg/d;各组药物总容量均配成20μl,CCI组注射等体积0.9%生理盐水。每组分别在术前、术后1、3、7、14 d给药30 min后,测定机械痛阈和热痛阈。于术后第7、14 d痛阈值测定后,分批提取大鼠L4~6节段脊髓（n=5/组）,应用免疫组化法检测脊髓背角Fos蛋白表达水平。结果：与Sham组相比,CCI组、Dex组、Suf组及DS组术后机械痛阈和热痛阈显著降低（P〈0.05）,术后7 d c-fos蛋白表达上调（P〈0.05）。与CCI模型组相比,Dex组、Suf组及DS组在术后3 d、7 d、14 d机械痛阈和热痛阈显著升高（P〈0.05）,c-fos蛋白表达水平在术后7 d差异显著（P〈0.05）。与DS组相比,Dex组及Suf组在术后3 d、7 d、14 d机械痛阈及热痛阈显著降低（P〈0.05）,c-fos蛋白在术后7 d表达显著增加（P〈0.05）。结论：鞘内联合应用右美托咪定及舒芬太尼治疗神经病理性疼痛具有显著的协调镇痛作用,能有效缓解CCI模型大鼠的机械痛敏及热痛敏。

Objective： To study the analgesic effect of dexmedetomidine combined with sufentanil intrathecal injection on CCI model of rats.Methods： Intrathecal catheters were successfully inplanted in 50 male SD rats.All the rats were randomly divided into five groups as follows： sham group（Sham）;model control group（CCI group）;dexmedetomidine group（Dex group）;sufentanil group（Suf group）;combined treatment group（DS group）.Rats in Dex group,Suf group and DS group were intrathecally injected respectively with dexmedetomidine 2 μg/（kg.d）,sufentanil 1 μg/d and dexmedetomidine 1 μg/（kg.d） ＋ sufentanil 0.5 μg/d daily at 1~14 d after CCI.The total capacity of each group of drugs was diluted into 20 μl,rats in CCI group were intrathecally injected with an equal volume of 0.9% saline daily.The paw mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） were measured 30 min after administration before operation and 1,3,7,and 14 days after CCI.Five in each group were sacrificed at 7 and 14 days after operation and the expressions of Fos protein in the dorsal root ganglion（DRG） were examined with the immunohistochemical methods.Results： The MWT and TWL at each time points were significantly decreased and c-fos protein expressions in DRG 7 days post-operation were significantly higher than group CCI,Dex,Suf and DS compared with group Sham（P 0.05）.MWT and TWL were significantly increased and c-fos protein expressions in DRG were significantly lower in group Dex,Suf and DS compared with group CCI（P 0.05）.MWT and TWL significantly increased and c-Fos protein expressions decreased in group DS compared with group Dex and Suf.Conclusion： Combined intrathecal application of dexmedetomidine with sufentanil could produce a significantly synergistic analgesic effects.