吗啡联合加巴喷丁对术后持续性痛大鼠脊髓小胶质细胞的影响  

EFFECTS OF INTRATHECAL COADMINISTRATION OF MORPHINE AND GABAPENTIN ON THE ACTIVATION OF SPINAL MICROGLIA IN PERSISTENT POSTOPERATIVE PAIN RATS

作　　者：胡兴国[1] 尹显和[2] 阳红艳[2] 张云翔[1] 曾因明[2] 

机构地区：[1]湖南省桃源县人民医院麻醉危重医学科,桃源415700 [2]徐州医学院江苏省麻醉与镇痛技术重点实验室.江苏省麻醉学重点实验室,徐州221002

出　　处：《中国疼痛医学杂志》2012年第8期489-494,共6页Chinese Journal of Pain Medicine

基　　金：湖南省科技计划一般项目资助课题(2009SK3018);江苏省教育厅开放研究课题(KJS1106)

摘　　要：目的:观察鞘内注射吗啡联合加巴喷丁对皮肤/肌肉切口和牵拉(skin/muscle incision and retraction,SMIR)术后持续性痛大鼠脊髓背角小胶质细胞活化的影响。方法:选择鞘内置管成功的雄性SD大鼠120只,随机分为5组(n=24):假手术组、术后持续性痛组、吗啡组、加巴喷丁组和吗啡联合加巴喷丁组。按Flatters法制作大鼠SMIR术后持续性痛模型;应用机械缩足反射阈值(mechanical withdrawal threshold,MWT)评定大鼠的疼痛行为学;应用免疫荧光技术检测脊髓背角活化的小胶质细胞标记物离子钙接头蛋白分子-1(ionized calcium bindingadaptor molecule-1,Iba-1)的表达。结果:与假手术组比较,术后持续性痛组的MWT在术后第3 d、7 d、12 d、22 d明显下降(P<0.05),脊髓背角Iba-1表达在术后第3 d、7 d明显增加(P<0.05);与术后持续性痛组比较,吗啡组和加巴喷丁组的MWT和脊髓背角Iba-1的表达无明显变化;与术后持续性痛,吗啡组和加巴喷丁组比较,吗啡联合加巴喷丁组的MWT在术后第3 d、7 d、12 d、22 d明显增加(P<0.05),脊髓背角Iba-1表达在术后第3 d、7 d明显减少(P<0.05)。结论:吗啡联合加巴喷丁对大鼠SMIR术后持续性痛有镇痛作用,可能与抑制脊髓背角小胶质细胞的活化有关。Objective： To study the effects of intrathecal coadministration of morphine and gabapentin on the activation of spinal microglia in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction （SMIR）. Methods： 120 male Sprague-Dawley rats were successfully implanted PE-10 catheter into the subarachnoid space （intrathecal） according to the Yaksh＇s method. 120 rats were randomly and evenly divided into five groups （n = 24）： sham operation group, persistent postoperative pain group, morphine group, gabapentin group and morphine combined with gabapentin group. A rat model of persistent postoperative pain evoked by SMIR was made according to the method described by Flatters. Mechanical withdrawal threshold （MWT） was assessed by yon Frey filament to determine pain sensitivity. The expression of ionized calcium bindingadaptor molecule-1 （Iba-1, a specific marker of microglia） in the spinal dorsal horn was detected by immunofluorescence at pre-operation and 3 d, 7 d, 12 d, 22 d and 32 d after operation. Results： Compared with sham operation group, the MWT in persistent post operative pain group decreased significantly at 3 d, 7 d, 12 d and 22 d after operation （P 〈 0.05）, the expression of Iba-1 in persistent postoperative pain group increased significantly at 3 d and 7 d after operation （P 〈0.05）; Compared with persistent postoperative pain group, the MWT and the expression of Iba-1 in the spinal dorsal horn in morphine group and gabapentin group did not change significantly at each time point; Compared with persistent post-operative pain group, morphine group and gabapentin group, the MWT in morphine combined with gabapentin group increased significantly at 3 d, 7 d, 12 d and 22 d after operation （P 〈 0.05）, the expression of Iba-1 in morphine combined with gabapentin group decreased significantly at 3 d and 7 d after operation （P 〈 0.05）. Conclusion： The analgesic effects of intrathecal coadministration of morphine and gabapentin may

关 键 词：疼痛 脊髓 加巴喷丁 吗啡 小胶质细胞 

分 类 号：R614[医药卫生—麻醉学]