TNF-α在坐骨神经冷冻致神经病理性疼痛模型大鼠脊髓的表达

摘要

Objective: To observe changes of behavior and expression of tumor necrosis factor-alpha (TNF-a) in the rat spinal cord after unilateral sciatic cryoneurolysis (SCN). Methods: 74 male SD rats were randomly divided into three groups: normal control group (n = 9), sham group (n = 27) and cryoneurolysis group (n = 38). Group C was divided into mechanical hyperalgesia (C28+) and non-mechanical hyperalgesia rats (C28-) by value of mechanical withdrawal threshold three weeks after operation. The mechanical withdrawal threshold and autotomy score were assessed before and 1, 2, 4 weeks after operation. Finally, TNF-a ELISA was performed on L4.6 spinal cord in 6 rats which were randomly selected at each timepoint. Results: One week after operation, operated rats exhibited significant elevation of mechanical withdrawal threshold on ipsilateral foot compared with that of pre-operation and group S. However, it went down gradually since then, and became much lower than that of pre-operation and group S 4 weeks after operation. Mechanical withdrawal threshold on contralateral foot in group C was lower than that of pre-operation and group S druing period after operation. Mechanical hyperalgesia was found only in group C, and the incidence on ipsilateral foot was higher than that on contralateral foot (35% versus 5%) 4 weeks after operation. Furthermore, autotomy score peaked in severity and incidence druing 1 to 2 weeks after SCN (18.4% for Is1 week and 24% for 2nd week respectively). Compared with group S and N, the bilateral spinal TNF-a expression in group C increased at different extent, especially more significantin hyperalgesia rats. Conclusion: TNF-a seems to play an important role in spinal cord pain processing andcentral sensitization after SCN.%目的:观察大鼠坐骨神经冷冻(SCN)后行为学及脊髓肿瘤坏死因子α(TNF-α)的表达变化.方法:74只SD大鼠随机分为3组:正常对照组(N组,n=9),假手术组(S组,n=27)和造模组(C组,n=38),C组根据术后3周时机械缩足阈测定值又分为机械痛敏组(C28+)和未出现机械痛敏组(C28-).各组在手术前及手术后1、2和4周进行机械缩足阈和自噬评分测定.每时间点随机取6只大鼠用酶联免疫吸附测定法(ELISA)测定脊髓腰膨大处的TNF-α表达.结果:术后1周时,C组术侧后足机械缩足阈较术前和S组显著增高(P＜0.01),随后逐渐下降,至术后4周时,机械缩足阈明显低于术前和S组水平(P＜0.05),而对侧后足机械缩足阈术后持续低于术前和S组(P＜ 0.05或P＜ 0.01).仅造模组出现机械痛敏,术后4周时,术侧痛敏发生率达35％,远高于对侧的5％(P=0.013).自噬仅发生于造模组术侧后足,在术后1周至2周内最为严重(术后1周发生率为18.4％,术后2周为24％).与S组和N组比较,C组术后各时间点双侧脊髓TNF-α表达均呈不同程度增加(P＜ 0.05或P＜0.01),尤以出现机械痛敏大鼠增加最为显著(P＜0.01).结论:脊髓TNF-α表达可能在冷冻致神经病理性疼痛中枢敏化中有重要作用.