杏仁核损毁对神经病理性疼痛大鼠疼痛症状及脊髓小胶质细胞活化的影响  

ALLEVIATION EFFECTS OF BASOLATERAL AMYGDALA LESIONS ON THE EVOKED HYPERSENSITIVITY AND SPINAL MICROGLIA ACTIVATION IN RATS WITH NEUROPATHIC PAIN

作　　者：杨冯睿[1] 罗晶晶[1] 彭良玉[1] 胡啸玲[1] 刘文捷[1] 

机构地区：[1]南华大学附属第一医院疼痛科麻醉科,衡阳421001

出　　处：《中国疼痛医学杂志》2015年第6期411-416,共6页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金项目(81300971);湖南省教育厅科研项目(14C0986)

摘　　要：目的：探讨损毁基底外侧杏仁核（Basolateral amygdala,BLA）对神经病理性疼痛大鼠疼痛症状及脊髓小胶质细胞活化的影响.方法：选择60只200～250 g纯种雄性SD大鼠,采用坐骨神经慢性缩窄手术（Chronic constriction injury,CCI）制备神经病理性疼痛模型,随机分为3组（n=20）：模型组（Model）,模型＋BLA损毁组（Model＋BLA lesions）和模型＋假手术组（Model＋sham）,模型＋ BLA损毁组于CCI术后7天采用立体定位辅助下将损毁电极插入BLA行阳级损毁.同时选取20只同周龄大鼠作空白对照组（Blank）,模型＋假手术组则仅行立体定位并插入未通电的损毁电极.观察各组CCI术前2d、术后1、4、7、11、14、17及21 d固定时间点的自发性痛行为,采用von Frey纤维和热辐射法分别测量以上时间点的机械性缩足反射阈值（Withdrawal mechanical threshold,MWT）和热刺激爪退缩阈值（Thermal withdrawal latency,TWL）;采用荧光免疫组化法检测术后21天脊髓大麻素受体2（Cannabinoid receptor 2,CB2）及特异表达补体C3受体（Complement receptor 3,OX-42）的荧光积分光密度（Integral opticaldensity,IOD）来评价脊髓小胶质细胞的活化情况;酶联免疫吸附法检测脊髓血浆肿瘤坏死因子（Tumor necrosis factor-α,TNF-α）和白介素-1β（interleukin-1β,IL-1β）水平来评价炎症反应情况.结果：与空白组相比,模型组的MWT和TWL水平降低,脊髓小胶质细胞CB2和OX-42的IOD增强及脊髓TNF-α和IL-1β水平升高;BLA损毁后可改善以上异常,模型＋BLA损毁组的MWT和TWL水平升高,脊髓小胶质细胞CB2和OX-42的IOD的增强及脊髓TNF-α和IL-1β水平的升高均被抑制,均优于模型组和模型＋假手术组（P＜0.05）,但与空白组的差异仍有统计学意义（P＜0.05）.结论：损毁BLA可改善神经病理性疼痛大鼠的疼痛症状,同时对脊髓小胶质细胞活化有抑制作用并降低炎症反应.Objective： To explore the possible alleviation effect of basolateral amygdala （BLA） lesions on neuropathic pain symptoms and spinal microglia activation in rats with neuropathic pain. Methods： Sixty male SD rats weighing 200-250 g were used to establish the neuropathic pain model following chronic constrictive injury （CCI） of nerves in rats. According to the experimental design, the neuropathic pain rats were randomly divided into 3 groups （n = 20）： model group, model ＋ BLA lesions group and model ＋ sham group. The rats in model ＋ BLA lesions group received the insertion of electrodes into the BLA followed by galvanization to damage the nuclei. Meanwhile, 20 SD rats of the same sex and age were chosen as blank control （blank group）. Blank group and model ＋ sham group were inserted with the electrodes into the BLA without galvanization to damage the nuclei. The spontaneous pain behavior was observed at a regular time 2 days pre-operative and day 1, 4, 7, 11, 14, 17 and 21 post-surgery. The von Frey fiber and thermal radiation were employed to measure the mechanical paw-withdrawal threshold （MWT） and thermal withdrawal latency （TWL） on the above time points. The immunohistochemistry was employed to evaluate the spinal microglia activation by the integral optical density （IOD） of C3 complement receptor （OX-42） and cannabinoid receptor 2 （CB2）. The spinal levels of TNF- α and IL-1β were measured by enzyme linked immunosorbent assay. Results： Compared with blank group, there were reduced MWT and shortened TWL, enhanced IOD of OX-42 and CB2, and increased level of TNF- α and IL- 1β in the model rats. After the damage of BLN, the above abnormalities were attenuated, as evidenced by the longer MWT and TWL but lower IOD of OX- 42 and CB2 and levels of TNF- α and IL-1β in model ＋ lesions group versus model group （P 〈 0.05）. Conclusions： BLN lesions exhibit a good analgesic effect on evoked hypersensitivity and inhibit spinal microglia activation and inflam

关 键 词：基底外侧杏仁核 神经病理性疼痛 疼痛症状 脊髓小胶质细胞活化 

分 类 号：R741[医药卫生—神经病学与精神病学]