电压门控钠离子通道β_3亚基下调缓解神经病理性疼痛

Knocking down of voltage gated sodium channel β_3 subunit could attenuate neuropathic pain

目的探讨电压门控钠离子通道β3亚基(SCN3B)在神经病理性疼痛中发挥的作用。方法成年SD大鼠50只,10只随机均分为RNA干扰组(R组)和对照组(C组),R组椎管内注射质粒,C组注射生理盐水,western blot鉴定质粒干扰效果。40只行坐骨神经分支选择结扎切断(spared nerve injury,SNI)模型制备,成功后的26只随机分为模型RNA干扰组(SR组)和模型对照组(SC组)。SR组分别在术后第7、9、11天椎管内注射SCN3B的短发夹RNA(Short Hairpin RNA,shRNA)质粒,第3次注药后7天检测。SC组,椎管内注射等量生理盐水,余操作相同。分别进行von Frey测试,观察背根神经节SCN3B表达下调对神经病理性疼痛引起的机械痛阈值降低程度的影响。结果 western blot结果表明R组大鼠的SCN3B表达量明显低于C组(P<0.05)。注射前,两组大鼠机械痛阈值差异无统计学意义。注射后,SR组的机械痛阈值为(7.23±1.74)g,明显高于SC组(2.31±0.46)g和注射前(1.60±0.23)(P<0.05)。结论背根神经节(dorsal root ganglion,DRG)的SCN3B的表达水平下调对神经病理性疼痛所致的痛觉过敏有一定的逆转作用,提示SCN3B参与神经损伤引起的神经病理性疼痛的发生。

Objective To explore the role of voltage gated sodium channel β3 subunit （SCN3B） plays in neuropathic pain. Methods Fifty adult SD rats were involved in the experiments. Ten rats randomly were divided into two groups： the RNA interference （group R） received intrathecal SCN3B interference plasmids and the control group （group C） received saline. The effects of interference were evaluated by western blot. Spared nerve injury （SNI） models were performed in the other 40 rats. 26 rats with significant mechanic allodynia were identified by von Frey tests. They were randomly divided into two groups： SNI model RNA interference group （group SR） and SNI model control group （group SC）. Rats in group SR were injected intrathecally with shRNA plasmids at 7,9,11 days after the SNI surgery while rats in group SC were injected intrathecally with saline. Von Frey tests were performed before and 7 days after the injections The results of two groups were observed to evaluate the effect of the downregulation of SCN3B in DRG on neuropathic pain behavior. Results The results of western blot demonstrated that the expression of SCN3B of group R were much lower than that of group C in DRG（P〈0. 05）. There was no difference with mechanical between the two groups before the injection. The mechanical threshold of group SR was （1.60±0. 23） g before the injections with SCN3B shRNA, and （7. 23±1.74） g after the injections. The mechanical threshold of group SC was （2.01±0. 33） g before the injections with saline, and （2.31 ±0. 46） g after the injections. Thus the mechanical threshold of group SR was obviously higher than the group SC after the injections（P〈0.05）. Conclusion The knockdown of SCN3B in DRG could attenuate neuropathie pain behavior, which indicated that SCN3B was involved in the progress of neuropathic pain.