鞘内注射氟柠檬酸对福尔马林致痛大鼠脊髓c-Fos和GFAP、OX42表达变化的影响

目的:通过鞘内注射氟柠檬酸(fluorocitrate,FCA)抑制脊髓胶质细胞功能后,对比观察足底注射福尔马林(formalin)模型大鼠热痛敏行为及脊髓后角c-Fos和胶质纤维酸性蛋白(glial fibrillaryacidic protein,GFAP)、OX42表达的变化,以探讨脊髓胶质细胞在痛觉过敏中的作用。方法:雄性SD大鼠40只,随机分为空白对照组(Blank组)、足底皮下注射生理盐水组(NS组)、足底皮下注射formalin组(F组)、鞘内注射生理盐水后皮下注射formalin组(NS+F组)、鞘内注射FCA后皮下注射formalin组(FCA+F组),每组8只。采用向大鼠右侧后肢足底皮下注射2.5%formalin(120μl)造成动物的伤害性刺激模型。造模后先测量记录各组大鼠的热刺激潜伏期(pawwithdrawalthermal latency,PWTL),然后灌注取脊髓组织切片进行抗c-Fos、抗GFAP和抗OX42标记的免疫组织化学染色。结果:足底注射formalin后,大鼠PWTL明显缩短,自发缩足反射次数明显增加,且在脊髓后角浅层有大量c-Fos、GFAP和OX42免疫产物表达;与blank照组和NS组比较,差异有统计学意义。而预先鞘内注射FCA再注射formalin后,大鼠PWTL明显延长,自发缩足反射次数明显减少(P<0.01),同时c-Fos、GFAP和OX42免疫产物表达亦明显降低(P<0.01),与F组和NS+F组比较差异有统计学意义。结论:抑制脊髓胶质细胞功能可明显减轻大鼠足底皮下注射formalin的痛觉过敏作用,脊髓胶质细胞主动参与了疼痛信息的调节作用。

EFFECTS OF INTRATHECAL ADMINISTRATION OF FLUOROCITRATE ON THE EXPRESSIONS OF C-FOS, GFAP AND OX42 IN SPINAL CORD OF RATS WITH FORMALIN-INDUCED PAIN

Objective: To study the effects intrathecal administration of fluorocitrate(FCA) on the paw-withdrawal thermal latency(PWTL) and the expressions of c-Fos,glial fibrillary acidic protein(GFAP) and OX42 in spinal cord of rats with formalin-induced pain.Methods: 40 male SD rats were randomly and evenly divided into 5 groups: blank group,normal saline(s.c.) injection into the hindpaw group(NS group),formalin(s.c.) injection into the hindpaw model group(F group),FCA(i.t) plus formalin(s.c.) model group(FCA+F group),NS(i.t) plus formalin(s.c.) model group(NS+F group),each group has 8 rats.The model rats were induced by subcutaneously(s.c.) injection 120 μl of 2.5% formalin into the right unilateral hindpaw.Then the animal’s behavior changes of PWTL,the expression of c-Fos,GFAP and OX42 in spinal cord were recorded.Results: After administration with formalin,the number of animal’s spontaneous flinching reflex was increased,the PWTL was shortened.At the same time,the expression of c-Fos,GFAP and OX42 were found in the superficial layer of dorsal horn of spinal cord.Compared with blank and NS group,the difference has statistics significance in F,FCA+F and NS+F groups.When pre-treated with FCA,the number of spontaneous flinching reflex was decreased,the PWTL was greatly lengthened,the expression of c-Fos,GFAP and OX42 were significantly decreased in the spinal cord.There was significant difference between the FCA+F group and the F,NS+F groups.Conclusion: Pre-inhibition of the glial functions reduces the thermal hyperalgesia induced by formalin injection into the hindpaw rats.The glial cells may actively take part in the regulating of pain signal transmission.