坐骨神经压迫性损伤大鼠背根神经节SNS/PN3钠通道表达的变化

Change of SNS/PN3 Na + channel expression in dorsal root ganglion neurons in the chronic constriction injury model of neuropathic pain

目的 通过观察背根神经节（DRG）电压门控钠通道SNS/PN3在大鼠坐骨神经压迫性损伤（CCI）的变化,以探讨慢性神经痛的发生机制。方法 对大鼠建立慢性神经痛模型,14d后,将神经痛模型大鼠18只,均分为6组,每组3只,组内同侧（CCI）与对侧自体对照（Control）,在深麻醉下快速断头,分别取L4和 L5 DRG,用Trizol试剂提取DRG总RNA。以逆转录多聚酶链反应（RT-PCR）半定量分析CCI后大鼠背根神经节钠通道SNS/PN3转录物的变化,以及全细胞膜片钳技术记录CCI对急性分离大鼠背根神经节TTX-R钠电流的影响。结果CCI术后14d,感觉神经元特异性的TTX-R钠通道转录物 SNS/PN3下调,与对照组相比,下降了大约60％,TTX-R钠电流密度明显减弱,但不影响其激活与稳态失活。结论 钠通道 SNS/PN3与慢性神经痛后初级感觉神经元过度兴奋有关。

Objective To investigate the changes in small-diameter sensory neuron (SNS)/ peripheral nerve type 3(PN3) Na+ channel transcript and in tetrodotoxin-resistant (TTX-R) Na+ current in dorsal root ganglion (DRG) neurons in a chronic constriction injury (CCI) model of neuropathic pain. Methods Eighteen rats were divided into 6 groups of 3 animals each. Chronic constriction injury model was established after Dib-Hajj et al. Pain threshold was significantly lowered after CCI as compared with that in control group. The animals were deeply anesthetized and rapidly decapitated 14 days after surgery. The L4-5 DRG of the operated side was removed and crushed and total RNA was extracted with trizol reagent. The DRG of the contralateral side was used as control. The change in SNS/PN3 Na + channel expression was determined by semi-reverse transcriptase-PCR. The DRG neurons were isolated enzymatically and the change in voltage-gated TTX-R Na+ current was recorded using whole-cell patch clamp technique. Results Sensory neuron specific TTX-R Na+ channel transcript SNS/PN3 was down-regulated by 60% 14 days after CCI as compared with that in control group. TTX-R Na+ current density was significantly reduced but its activation and steady state inactivation were unchanged. Conclusions Na+ channel SNS/PN3 is involved in the hyperextability of the primary sensory neurons after CCI.