目的探讨低频电针干预早期神经痛背根神经节(dorsal root ganglion,DRG)辣椒素受体(Transient receptor potential vanilloid type 1,TRPV1)的机制。方法将32只大鼠随机分为正常组、假手术组、模型组与电针组,每组8只。采用脊神经结扎的方法制作大鼠神经痛模型。取患侧足三里、昆仑穴进行2 Hz电针治疗,连续3 d。检测大鼠术侧后足缩腿阈(Paw withdrawal threshold,PWT),L5 DRG TRPV1表达与磷酸化水平。进一步开展PKC激动剂PMA与PKA激动剂db-cAMP拮抗2 Hz电针镇痛作用的验证性实验。结果 SNL模型大鼠早期即出现自发性疼痛,PWT显著下降(P〈0.001),L5 DRG TRPV1表达水平降低(P〈0.01),磷酸化水平升高(P〈0.001)。SNL假手术组大鼠PWT没有显著变化。2 Hz电针能提高SNL模型大鼠的PWT(P〈0.001),降低L5 DRG TRPV1磷酸化水平(P〈0.05)。PMA与db-cAMP足部局部注射能拮抗2 Hz电针的抗神经痛作用(P〈0.001,P〈0.001)。结论早期神经痛与损伤DRG TRPV1磷酸化水平升高有关。低频电针能改善早期神经痛,可能与下调损伤DRG的TRPV1磷酸化水平有关。
Objective To investigate the dorsal root ganglion (DRG) capsaicin receptor (transient receptor potential vanilloid type 1, TRPV1)-involved mechanism of low-frequency electroacupuncture in alleviating early neuropathic pain. Methods Thirty-two rats were randomly allocated to normal, sham operation, model and electroacupuncture groups, 8 rats each. A rat model of neuropathic pain was made by spinal nerve ligation. Points Zusanli and Kunlun on the affected side were selected for three consecutive days of treatment with 2 Hz electroacupuncture. Operated side hind paw withdrawal threshold (PWT), and L5 DRG TRPV1 expression and phosphorylation levels were measured in the rats. The antagonistic effects of PKC agonist PMA and PKA agonist db-cAMP on 2 Hz electroacupuncture analgesia were further validated. Results Spontaneous pain occurred in the early stage, and PWT lowered markedly (P〈0.001), L5 DRG TRPV1 expression levels fell (P〈0.01) and L5 DRG TRPV1 phosphorylation levels rose (P〈0.001) in a rat model of SNL. PWT did not change in the sham SNL group of rats. 2 Hz electroacupuncture raised PWT (P〈0.001) and lowered L5 DRG TRPV1 phosphorylation levels (P〈0.05) in a rat model of SNL. Local injection of the foot with PMA and db-cAMP inhibited the alleviating effect of 2 Hz electroacupuncture on neuropathic pain (P〈0.001,P〈0.001). Conclusions Early neuropathic pain is related to a rise in TRPV1 phosphorylation levels in the injured DRG Low-frequency electroacupuncture can relieve early neuropathic pain, which may be related to the down-regulation of TRPV1 phosphorylation levels in the injured DRG.