下丘脑室旁核胶质细胞活化在大鼠炎性痛调节过程中的作用

Role of hypothalamic paraventricular nucleus glial activation in regulating inflammatory pain in rats

目的探讨下丘脑室旁核胶质细胞活化在大鼠炎症性疼痛发生、发展过程中的作用。方法健康成年♂SD大鼠(230~250 g),通过左侧后肢足底中心皮下注射完全弗氏佐剂(complete Freund’s adjuvannt,CFA)建立炎症性疼痛模型,通过免疫荧光技术检测下丘脑室旁核小胶质细胞和星形胶质细胞活化情况;室旁核给予小胶质细胞特异性抑制剂米诺环素后,通过测定大鼠热缩足潜伏期(thermal withdrawal latency,TWL)观察热痛行为变化。结果 (1)与生理盐水对照组相比,CFA组大鼠室旁核小胶质细胞于d 1开始明显活化,直至d14仍处于活化状态;星形胶质细胞于d3开始明显活化,直至d 14仍处于活化状态;(2)与生理盐水组相比,CFA致炎后d 1,通过室旁核微量注射,米诺环素组大鼠于给药后1、2、3 h热痛敏均明显减轻,TWL明显升高(P<0.05);(3)CFA致炎后d6,与室旁核微量注射生理盐水组相比,米诺环素组大鼠于给药后各时间点热痛敏无明显改变;并在给药后2 h室旁核小胶质细胞活化水平明显降低,星形胶质细胞活化无明显改变。结论小胶质细胞活化参与了CFA所致的慢性炎症性疼痛的发生过程,而对慢性炎症性疼痛的发展过程可能无明显作用。

Aim To investigate the role of glial cell activation in the paraventricular nucleus of the hypothalamus（PVN） in the genesis and development of inflammatory pain in rats. Methods Healthy adult male SD rats（230 ~ 250 g） were chosen to establish the model of inflammatory pain through subcutaneous injection of complete Freund＇s adjuvant（CFA） on the center of left hind foot. The activation of microglia and astrocytes in the PVN was detected by immunofluorescence technique. After the microinjection of microglia specific inhibitor minocycline into paraventricular nucleus,thermal withdrawal latency（TWL） was measured to observe the changes of heat pain behavior in rats. Results（1） Compared with normal saline control group,microglia in the paraventricular nucleus in CFA group was significantly activated in d 1 and still in activated state until d 14. Astrocytes began to be significantly activated in d 3,and was still in activated state until d14.（2） On d 1 after CFA induced inflammation,compared with PVN microinjection of normal saline,heat hyperalgesia was significantly alleviated,and TWL increased markedly after 1 h,2 h and 3 h in PVN administration of minocycline（P〈0. 05）.（3） On d 6 after CFA induced inflammation,compared with PVN microinjection of normal saline,heat hyperalgesia did not change significantly in each time point after administration of minocycline; and the activation level of microglia in paraventricular nucleus significantly decreased after 2 h in PVN administration of minocycline; the activation of astrocytes did not change significantly. Conclusions The activation of microglia in the PVN may be involved in the genesis of chronic inflammatory pain induced by CFA; however,there may be no obvious effect on the development of chronic inflammatory pain.