神经病理性疼痛大鼠脊髓星形胶质细胞增殖活化的变化

GUal activation in spinal cord in a rat model of neuropathic pain

目的观察神经病理性疼痛大鼠脊髓星形胶质细胞增殖活化的变化。方法健康成年雄性SD大鼠48只,随机分为假手术组和手术组(n=24),慢性坐骨神经挤压损伤(CCI)前1d、CCI后1、4、7、14、28 d各随机取4只大鼠,测定机械痛阈和热痛阈后立即处死大鼠,取L_(4,5)脊髓,用免疫组化方法观察胶质纤维酸性蛋白(GFAP)表达以反映星形胶质细胞激活情况。结果CCI后1 d术侧机械痛阈和热痛阈开始下降,机械痛阈CCI后7 d下降至最低,热痛阈CCI后4 d下降至最低,CCI后28 d仍处于较低水平(P＜0．05或0．01)；手术组术侧脊髓后角GFAP表达于CCI后4 d开始增加,至CIC后7 d达高峰,至CCI后28 d仍维持于高水平(P＜0．05)。结论脊髓星形胶质细胞的增殖活化参与神经病理性疼痛的发生和维持。

Objective To investigate the response of astrocytes in lumbar spinal cord in a rat model of chronic constrictive injury （CCI）. Methods Forty-eight male SD rats weighing 220-280 g were randomly divided into 2 groups （ n = 24 each） ： group Ⅰ CCI and group Ⅱ sham operation. CCI was produced by placing 4 loose ligatures on the right sciatic nerve at 1 mm intervals with 4-0 chromic catgut. The threshold to von Frey filament and to radiant heat stimulation were measured before operation （baseline） and at 1, 4, 7, 14 and 28 d after operation. Four animals were killed at each time point and lumbar segment of spinal cord was removed for determination of glial fibrillary acidic protein （GFAP） in the astrocytes in spinal cord by immuno-histochemical assay. Results The threshold to mechanical and thermal stimuli started to decrease at 1 d after operation （CCI）. Mechanical and thermal hyperalgesia peaked at 7 d and 4 d after operation respectively and persisted until the end of experiment. Immuno-histochemical assay demonstrated that GFAP positive astrocytes in the dorsal horn on the operated side significantly increased at 4 d after operation and reached the peak at 7 d and was maintained at a high level until the end of experiment. Conclusion Glial activation is involved in the mechanism of neuropathic pain.