细胞因子参与EPO预防神经病理性疼痛的机制探讨

An investigation of underlying mechanism for recombinant human erythropoietin to prevent neuropathic pain in rats

目的探讨预防性给予重组人红细胞生成素(rhEPO)对神经病理性疼痛大鼠模型机械、热痛觉高敏的影响及可能的机制。方法雄性SD大鼠30只随机均分成三组。A、B组切断L5脊神经建立大鼠神经病理性疼痛模型;C组为假手术对照。术前1d,A组腹腔注射rhEPO 5000U/kg,连续7d;B组腹腔注射生理盐水作为模型对照。采用von Frey仪测定各组0、3和7d机械缩足反射阈值;术后第7天用ELISA法测定大鼠L5脊髓组织TNF-α、IL-1β、IL-6和IL-10表达。结果与C组相比,A、B组大鼠L5脊神经损伤术后,术侧均出现明显的机械痛阈下降(P<0.01);但A组大鼠的机械痛高敏行为较B组明显缓解(P<0.01)。与C组比较,大鼠脊髓TNF-α、IL-1β、IL-6和IL-10表达明显增高(P<0.01);与B组比较,A组脊髓组织IL-6水平明显降低,而IL-10水平明显升高(P<0.01)。结论 rhEPO能预防模型大鼠神经病理性疼痛的发生,其效应与减少促炎细胞因子和增加抗炎细胞因子释放有关。

Objective To investigate the effect and underlying mechanism for recombinant human erythropoietin（rhEPO） to prevent neuropathic pain in rats. Methods Thirty male SD rats were equally randomized into three groups. The neuropathic pain models were established by L5 nerve transection in groups of A and B. The rats in group C were taken as sham operation controls, rhEPO 5000 U/kg was injected intraperitoneally onece a day fir 7 days and normal saline instead of rhEPO was used in group B. The hind paw mechanical withdrawal threshold（MWT） was measured with von Frey filament on the 0, 3rd and 7th day after operation. The expressions of tumor necrosis factor-α （TNF-a）, interleukin（IL）-lβ, IL-6 and IL-10 in the L5 spinal cord were detected using ELSIA on the 7th day after operation. Results Compared to group C, the pain threshold to mechanical stimulation was decreased significantly after L5 nerve transection in groups of A and B（P〈0. 01）. Compared to group B, mechanical hyperalgesia in group A was attenuated significantly（P〈0. 01）. The expressions of TNF-α,IL-1β,IL-6 and IL-10 in the Ls spinal cord were higher in groups of A and B than thoae in group C（P〈0. 01）. The expression of IL-6 was lower,but that of IL-10 was higher, in group A than that in group B（P〈0. 01）. Conclusion rhEPO has a potential preventive effect on neuropathic pain in rats, which is related to its inhibitory effect on proinflammatory cytokines and promoting release of antiinflammatory cytokines in the spinal cord.