小胶质细胞在偏头痛大鼠中枢敏化过程中的作用

摘要

目的 观察二甲胺四环素(MC)对偏头痛大鼠痛觉超敏行为、颈髓后角小胶质细胞及神经元激活的影响,探讨小胶质细胞在偏头痛大鼠模型中枢敏化过程中的作用.方法 66只雄性SD大鼠随机分为空白组、假手术组、生理盐水组(NS组)、新型致炎剂(IS)4 d组(IS4组)、IS7 d组(IS7组)、IS/MC预防组、IS/NS预防组、NS/NS预防组、IS/MC治疗组、IS/NS治疗组、NS/NS治疗组.每组6只.采用Vonfrey纤维丝测定各组大鼠眶周痛觉阈值,免疫荧光染色测定颈髓后角小胶质细胞及神经元激活情况.结果 硬脑膜给予IS第3天眶周痛觉阈值较NS组明显下降(P＜0.01).IS/MC预防纽眶周痛觉阈值明显高于IS/NS预防组(P＜0.01).IS4组、IS7组小胶质细胞平均荧光密度值高于假手术组(P＜0.01).IS/MC预防组、IS/MC治疗组小胶质细胞平均荧光密度值分别低于IS/NS预防组、IS/NS治疗组(P＜0.01).IS/MC预防组C-fos平均荧光密度值明显低于IS/NS预防组(P＜0.01).结论 在慢性硬脑膜炎症所致的中枢敏化过程中小胶质细胞可能仅在启动阶段起作用,对于痛觉超敏的维持无作用.MC能有效预防偏头痛大鼠模型痛觉超敏的发生,但对已存在的痛觉超敏无治疗作用.%Objective To study the role of microglia in central sensitization of rats with migraine by obsering the effect of minocycline(MC) on their hypersensitive behaviors and activation of microglia and neurons in their cervical spinal cord posterior horns. Methods Sixty-six male SD rats were randomly divided into blank group,sham operation group,saline group(NS group),new inflammatory soup 4 d group(IS4 group), new inflammatory soup 7 d group(IS7 group),IS/MC prevention group,IS/NS prevention group,NS/NS prevention group,IS/MC treatment group,IS/NS treatment group,NS/NS treatment group(6 in each group). Their periorbital pressure threshold was measured by von Frey filament assay. Activation of microglia and neurons in their cervical spinal cord posterior horns was detected with immunofluorescence staining. Results The periorbital pressure threshold was significantly lower on day 3 after new IS infusion through the dura mater of brain than after saline infusion and significantly higher in IS/MC prevention group than in IS/NS prevention group(P<0. 01). The average OD of microglia was significantly higher in IS4 group and IS7 group than in sham operation group and significantly lower in IS/MC prevention group and IS/MC treatment group than in IS/NS prevention group and IS/NS treatment group (P<0. 01). The average OD of C-fos was significantly lower in IS/MC prevention group than in IS/NS prevention group(P<0. 01). Conclusion Microglia may play a role in the initial chronic dural inflammation-induced central sensitization but not in maintenaning hyperalgia. MC can effectively prevent hyperalgia in a model of rats with migraine but has no effect on hyperalgia.