脊髓胶质细胞在大鼠炎性痛形成中的作用

目的 评价脊髓胶质细胞在大鼠炎性痛形成中的作用.方法 清洁Ⅱ级成年雄性SD大鼠,体重180～220 g,取蛛网膜下腔置管成功的大鼠65只,随机分为5组(n=13),生理盐水组(NS组):右后肢踝关节外侧皮下注射NS 50μl;炎性痛组(IP组):采用右后肢踝关节外侧皮下注射完全弗氏佐剂50μl的方法制备炎性痛模型;氟代柠檬酸组(FC组):经蛛网膜下腔导管注射FC 1 nmol/10 μl,15 min后右后肢踝关节外侧皮下注射NS 50 μl;NS+IP组:经蛛网膜下腔导管注射NS 10 μl,15 min后制备炎性痛模型;FC+IP组:经蛛网膜下腔导管注射FC 1 nmol/10 μ,15 min后制备炎性痛模型.于模型制备前2 d(T_0)、皮下注射药物前(T_1)和注射药物后2、4、6、8、10、12、24、26 h(T_(2～9))时测定机械缩足阈值(MWT)和热缩足潜伏期(TWL).皮下注射药物后8 h时采用免疫组化法测定脊髓背角星形胶质细胞标记物(GFAP)和小胶质细胞标记物(OX-42)的表达水平.结果 与NS组比较,IP组和NS+IP组T_(3～9)时MWT和TWL降低,FC+IP组T_(3～9)时MWT降低,T_(8,9)时TWL降低,IP组、NS+EP组和FC+EP组脊髓GFAP和OX-42的表达水平均上调(P<0.05);与IP组比较,FC组T_(3～9)时MWT和TWL升高,FC+IP组T_(3～7)时MWT和TWL升高,2组脊髓GFAP和OX-42的表达水平均下调(P<0.05或0.01).结论 脊髓胶质细胞的活化参与了大鼠炎性痛的形成.

Role of gliocytes in the spinal cord in development of inflammatory pain in rats

Objective To evaluate the role of gliocytes in the spinal cord in the development of inflammatory pain (IP) in rats. Methods Adult male SD rats weighing 180-220 g were used in this experiment. A catheter was implanted in the subarachnoid space according to the method described by Yang. Animals with abnormal motor function of the hindlimb after intrathecal (IT) catheter implantation were excluded. IP was induced by subcutaneous (sc) injection of complete Freund's adjuvant (CFA) 50 μl at the lateral side of the ankle joint of the right hindpaw. Sixty-five rats were randomly divided into 5 groups ( n = 13 each): group I IP control normal saline (NS) 50μl was injected sc instead of CFA; group II IP; group IE PC (IT) + IP control fluorinated citric acid (FC, a gliocyte metabolism inhibitor) 1 nmol/10μl was injected IT at 15 min before NS 50 μl sc injection; group IV NS (IT) + IP and group V FC (IT) + IP. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before induction of IP (T_0, baseline) .before and at 2, 4, 6, 8, 10, 12, 24 and 26 h (T_(1-9)) after sc NS or CFA injection. Five enimals in each group were killed at T_5 (8 h after sc NS/CFA injection) and the lumbar segment (L_(4,5)) was removed for determination of glial fibrillary acidic protein ( CFAP) and OX-42 expression by immuno-histochemistry. Results In group Ⅱ and Ⅳ sc CFA significantly decreased MWT and TWL. Mechanical and thermal hyperalgegia induced by sc CFA was significantly suppressed by intrathecal FC in group V . IP significantly increased GFAP and OX-42 expression in the spinal cord. Intrathecal FC significantly attenuated IP-induced up-regulation of GFAP and OX-42 expression in the spinal cord. Conclusion The activation of gliocytes in the spinal cord is involved in the development of CFA-induced hyperalgesia in rats.