推拿对神经病理性疼痛大鼠的镇痛作用及其机制

Analgesic effect of massage on rats with neuropathic pain and its mechanism

目的探讨推拿对神经病理性疼痛(NPP)大鼠的镇痛作用及其机制。方法将30只SD大鼠随机分为正常组、脊神经结扎(SNL)组、假手术组、推拿组、假推拿组,每组6只。除正常组和假手术组外,其余3组均建立SNL模型。于术后第1天开始对推拿组、假推拿组进行干预,连续干预7 d,其余3组不予干预。于术前、术后1 d、术后3 d和7 d测定各组大鼠的热痛缩足反应潜伏期(PWTL)和机械性刺激缩足阈值(PWMT);于术后第7天检测大鼠L_(4~6)脊髓组织BRAF活化的非编码RNA(BANCR)的表达水平、L_(5)脊髓组织微管相关蛋白轻链3(LC3)和p62蛋白的表达水平、血清白细胞介素1β(IL-1β)的表达水平。结果(1)术后1 d、3 d、7 d,SNL组、推拿组的PWTL和PWMT均较正常组降低,术后3 d、7 d,推拿组的PWTL和PWMT均较SNL组升高(均P<0.05)。(2)术后7 d,SNL组的血清IL-1β表达水平、脊髓组织BANCR表达水平、p62蛋白表达水平均较正常组升高,脊髓组织LC3Ⅱ蛋白表达水平较正常组降低,推拿组的血清IL-1β表达水平、脊髓组织BANCR表达水平、p62蛋白表达水平均较SNL组降低,脊髓组织LC3Ⅱ蛋白水平较SNL组升高(均P<0.05)。结论推拿可减轻SNL大鼠的痛觉过敏反应,其可能通过抑制BANCR的表达,以及上调自噬相关蛋白LC3表达和下调p62蛋白表达,从而激活自噬,清除促炎因子IL-1β的堆积,进而达到阻断神经传导的作用。

Objective To explore the analgesic effect of massage on rats with neuropathic pain(NPP)and its mechanism.Methods Thirty SD rats were randomly divided into normal group,spinal nerve ligation(SNL)group,sham operation group,massage group,or sham massage group,with 6 rats in each group.Except for the normal group and the sham operation group,the SNL model was established in the remaining 3 groups.The intervention was given to the massage and sham operation groups on the first day after operation for continuously 7 days,and the remaining 3 groups did not receive intervention.The paw withdrawal thermal latency(PWTL)and paw withdrawal mechanical threshold(PWMT)of rats in each group were measured before operation,1,3 and 7 days after operation;furthermore,the expressions of L_(4-6) spinal tissues BRAF-activated non-coding RNA(BANCR),microtubule associated protein light chain 3(LC3)and p62 proteins in L_(5) spinal tissues,and serum interleukin 1β(IL-1β)were detected in the rats on the 7^(th) day after operation.Results(1)The SNL and massage groups exhibited lower PWTL and PWMT as compared with the control group 1,3,and 7 days after operation,and the PWTL and PWMT were higher in the massage group than those in the SNL group 3 and 7 days after operation(all P<0.05).(2)The SNL group interpreted elevated expressions of serum IL-1β,BANCR and p62 protein in spinal tissues,whereas a decline of LC3Ⅱprotein expression in spinal tissues as compared with the normal group 7 days after operation;in addition,the massage group depicted decreased expressions of serum IL-1β,BANCR and p62 protein in spinal tissues,whereas an elevation of LC3Ⅱprotein expression in spinal tissues as compared with the SNL group(all P<0.05).Conclusion Massage can alleviate the hyperalgesia of SNL rats,which may activate autophagy and clear the accumulation of pro-inflammatory factor IL-1βthrough inhibiting BANCR expression,up-regulating autophagy associated protein LC3 expression,and down-regulating p62 protein expression,so as to exert an effect of blocking nerve conduction.