中脑导水管周围灰质小胶质细胞活化在大鼠神经病理性痛中的作用

Role of activation of microglias in midbrain periaqueductal gray in neuropathic pain in rats

目的评价中脑导水管周围灰质小胶质细胞活化在大鼠神经病理性痛中的作用。方法雄性sD大鼠176只，体重200～250g，9周龄，采用随机数字法，将其分为4组：假手术组（s组，n=40）、神经病理性痛组（NP组，n=40）、生理盐水组（Ns组，n=48）和米诺环素组（M组，n=48）。NP组、Ns组和M组采用慢性坐骨神经缩窄性损伤法制备大鼠神经病理性痛模型；s组仅暴露坐骨神经，而不结扎。术后第7天时，Ns组和M组分别于中脑导水管周围灰质的腹外侧区注射生理盐水或米诺环素0．5μ1。取8只大鼠，分别于术前1d（T0）、术后第3天（T^1）、第7天给药前30min（T2）、第7天给药后30min（T3）、第14天（T4）和第21天（T5）时测定机械痛阂。于T1-5时各处死8只大鼠，取脑组织，行小胶质细胞计数。结果与S组比较，NP组、Ns组和M组T1-5，时机械痛阈降低，小胶质细胞计数升高（P〈0．05）；NP组和Ns组各时点机械痛阈和小胶质细胞计数差异无统计学意义（P〉0．05）；与NP组和Ns组比较，M组T3时机械痛阈升高，小胶质细胞计数降低（P〈0．05）。结论中脑导水管周围灰质小胶质细胞的活化参与了大鼠神经病理性痛中的形成与维持。

Objective To evaluate the role of activation of microglias in midbrain periaqueductal gray in neuropathic pain （NP） in rats. Methods One hundred and seventy-six male Sprague-Dawley rats, weighing 200- 250 g, aged 9 weeks, were randomly divided into 4 groups： sham operation group （group S, n = 40）, group NP （ n = 40） , normal saline group （group NS, n = 48） and minocycline group （group M, n = 48） . The rats were anesthetized with intraperitoneal 4% chloral hydrate 300 mg/kg. NP was induced by chronic constrictive injury in groups NP, NS and M. Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread. Sciatic nerve was only exposed but not occluded in group S. M inocycline and nor- mal saline 0. 5 μl were injected into the ventrolateral periaqueductal gray in groups M and NS, respectively, at 7 days after operation. Eight rats were chosen in each group and the mechanical pain threshold was measured at 1 day before operation （T0）, 3 days after operation （T1）, 30 min before and after administration on 7 days after op- eration （T2-3 ）, and 14 and 21 days after operation （T4-5）. Eight animals were sacrificed at T1-5 in each group and brains were removed for determination of microglia counts in brain tissues. Results Compared with group S, the mechanical pain threshold was significantly decreased and microglia counts were increased at T1-5 in groups NP, NS and M （P 〈 0.05）. There was no significant difference in the mechanical pain threshold and microglia counts at each time point between groups NP and NS （P 〉 0.05）. Compared with groups NP and NS, the mechanical pain threshold was significantly increased and microglia counts were decreased at T3 in group M （ P 〉 0.05 ）. Conclu-sion Activation of microglias in midbrain periaqueductal gray is involved in the development and maintenance of NP in rats.