c-fos反义寡核苷酸探针对大鼠炎性痛和神经病理性痛的影响

Effects of c-fos antisense oligodeoxynucleotides on inflammatory and neuropathic pain of rats

研究c-fos反义寡核苷酸探针(antisense oligodeoxynucleotides,ASO)对大鼠炎性痛和神经病理性痛的作用效果,为临床慢性疼痛的治疗提供理论依据。以大鼠足底注射福尔马林(formalin)致炎性痛模型和腰5脊神经结扎(spinal nerve ligation,SNL)诱导神经病理性痛模型为基础,分别观察鞘内给予c-fosASO对两种模型大鼠的行为学及腰5脊髓背角Fos阳性神经元表达的影响。行为学检测结果表明:和正义探针(SO)组以及生理盐水(NS)对照组相比,鞘内预先给予c-fosASO后,大鼠足底注射福尔马林引起自发缩足反射次数和SNL诱导的机械性缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL)均有明显缓解(P<0.05),而c-fosASO不能逆转SNL诱导的神经病理性痛。免疫荧光组织化学染色结果发现:和对照组相比,鞘内给予c-fosASO能显著抑制福尔马林和SNL诱导的大鼠腰髓背角Fos阳性神经元的增加。上述结果提示,脊髓背角c-fos的活化对于炎性痛和神经病理性痛的发展都有显著意义,而抑制其活化在预防阶段比治疗阶段对慢性疼痛的缓解作用更为显著。

The present research was to investigate the effects of intrathecal administration of c-fos antisense oligodeoxynucleotides （ASO） on inflammatory, and neuropathic pain of rats, and thus would supply some theoretical evidence for the clinical treatment of chronic pain. Basing on the formalin induced inflammatory pain model and L5 spinal nerve ligation （SNL） induced neuropathic pain model, we investigated the behavioral change and the expression of Fos positive neurons after intrathecal administration of c-fos ASO. The behavioral results indicated that, compared to the SO and saline groups, pretreatment ofc-fos ASO significantly altered the formalin induced spontaneous flinches and mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） induced by SNL. While c-fos ASO could not reverse SNL induced neuropathic pain. Immunofluorescent histochemistry indicated that the expression of Fos positive neurons induced by formalin or SNL were significantly reduced after c-fos ASO administration. The above results indicate that the activation of c-fos is of great importance for the inflammatory and neuropathic pain. And it is more meaningful to suppress its activation in the preventing than the treating stage.