颈背根节神经元异位自发放电增强诱致大鼠慢性颈椎根性痛的作用机制研究

Enhancement of ectopic spontaneous discharges of cervical DRG neurons contribute to the development of cervical radiculopathic pain in rats

目的：建立慢性压迫颈背根神经节诱致的颈椎根性痛（cervical radiculopathic pain,CRP）模型,观察颈背根节神经元产生异位自发放电诱致颈椎根性痛的作用。方法：采用体重为100~150 g的成年SD大鼠,在椎间孔内植入L型不锈钢钢柱形成慢性压迫C7/C8背根节,建立颈椎根性痛模型。用Von Frey细丝刺激大鼠前足足底来检测机械痛敏。用热辐射刺激仪刺激大鼠前足足底来检测热痛敏,其热缩足反射潜伏期由自动计时器读出。用丙酮刺激大鼠前足足底来观察冷刺激反应级别;同时检测大鼠前足肌肉的瞬间肌力;进行在体C7/C8 DRG背根纤维胞外电生理记录。结果：（1）CRP大鼠损伤侧前足表现出对机械刺激、热刺激以及冷刺激明显的痛觉过敏现象。（2）在C7/C8 DRG慢性压迫损伤后有62.7%的神经元发生异位自发放电,而对照组只有22.5%的神经元发生自发放电。与对照组相比,CRP组发生异位自发放电的比例明显增加。受损神经元的自发放电呈现三种不同的放电模式,即阵发性放电,周期性放电以及非周期性放电。结论：我们通过对C7/C8 DRG神经元施加稳固的慢性机械压迫建立了一个新的CRP模型,CRP大鼠表现出明显的痛行为学过敏反应。这种痛觉过敏可能由受损DRG神经元异位自发放电增强介导。

Objective： To establish a cervical radiculopathic pain（ CRP） model induced by chronic compression of cervical DRGs and to explore the underlying mechanisms of cervical radiculpathic pain mediated by ectopic spontaneous discharges in injured cervical DRG neurons. Methods： Adult Sprague-Dawley rats weighing 100-150 g were subjected to CRP operation. A fine,stainless L-shaped steel rod was inserted into intervertebral foramen for steady compression of C7 /C8 DRGs. Mechanical sensitivity was tested with manual application of Von Frey hairs to the plantar surface of rat forepaw. Thermal sensitivity was tested by application of infrared heat to the plantar surface of forepaw and the response latency was measured from an automated device readout. Cold allodynia was examined by application of acetone to the plantarsurface of forepaw. In parallel,grid strength of forepaw muscle was tested. Extracellular electrophysiological recordings from C7 / C8 myelinated dorsal root fibers were performed in vivo. Results：（ 1） CRP rats displayed marked mechanical and thermal hyperalgesia as well as cold allodynia in the injured forepaw of the rat.（ 2） Ectopic spontaneous discharges were present in 62. 7% of the fibers recorded from DRG neurons injured with chronic compression in contrast to 22. 5%from uninjured DRG. The rate of spontaneous ectopic discharges was significantly increased in CRP rats compared to controls. Patterns of spontaneous firing fell into three types,i. e. bursting,periodic and irregular firing. Conclusion： Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion（ DRG）,which induces dramatic behavioral pain hypersensitivity. This exaggerated pain hypersensitivity was at least in partial mediated by the spontaneous ectopic discharges in injured DRG neurons.