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

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

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。

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 ~tl 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. Whenpre-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.