大鼠慢性背根节压迫诱致DRG大神经元兴奋性增强和I_h电流显著上调

目的:探讨大鼠CCD模型模拟的腰背痛诱致的DRG大神经元兴奋性改变及其离子通道机制。方法:建立大鼠慢性压迫腰膨大L4/L5 DRG的CCD模型,模拟临床常见的腰背痛的触诱发痛表现。制备整节L4/L5 DRG标本,应用全细胞膜片钳技术记录去极化电流刺激诱致的DRG大型神经元的兴奋性改变及其离子通道机制。结果:对直径50μm的健康的DRG大神经元进行全细胞膜片钳记录。结果显示:给予去极化方波电流刺激可以诱致CCD模型大鼠DRG大神经元呈现兴奋性增强的表现,具体表现为相同刺激强度的电流注射在CCD模型DRG大神经元上诱致的动作电位的频率显著高于对照组神经元。同样的细胞放电增强也见于给予细胞斜波电流刺激。进一步的机制研究分析显示CCD模型大鼠上DRG大神经元的I_h电流明显高于对照组大鼠。结论:CCD模型可以诱致DRG大神经元呈现超兴奋状态,该兴奋性增强的状态主要由I_h电流增强来介导,为认识神经损伤诱致的病理性痛觉敏化尤其是触诱发痛的神经机制提供了实验证据。

Chronic compression of dorsal root ganglion induces hyperexcitability and upregulation of Ih current in large DRG neurons of rats

Objective:To explore the changes of excitability in large DRG neurons of rats induced by chronic compression of dorsal root ganglion (CCD) aiming to mimic low back pain and its underlying ionic mechanisms.Methods:Chronic compression of L4/L5 DRG models of rats were established to mimic the symptoms of low back pain in clinic.By using whole-cell patch-clamp recording techniques in intact L4/L5 DRG preparation,the excitability of large DRG neurons and its ionic basis was examined.Results:Large DRG neurons with diameter more than 50 μm were recorded.The present study demonstrated that large DRG neurons derived from CCD rats displayed increased excitability,manifesting as enhanced action potential frequency in response to depolarizing current injection as compared to sham controls.Similar hyperexcitability was seen in response to ramp current injection.Further studies showed that Ih current was greatly enhanced in CCD group as compared to sham group.Conclusion:CCD induces hyperexcitability in large DRG neurons,which is mainly mediated by upregulation of Ih current.This study provides for under sranding of the mechanical allodynia associated with nerve injury.