Liu Baogang, Eisenach James C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Neurophysiol. 2005 Nov;94(5):3159-67. doi: 10.1152/jn.00623.2005.
Hyperexcitability after peripheral nerve injury occurs in axotomized and neighboring unaxotomized dorsal root ganglion (DRG) neurons and contributes to hypersensitivity. Previous studies have focused on proximal nerve injury and have not examined unaxotomized neurons innervating the site of sensory testing. The current study used a distal nerve injury (partial sciatic nerve ligation [PSNL]), and identified, using fluorescent tracers, axotomized and unaxotomized neurons innervating the site of hypersensitivity. We hypothesized that reduced hypersensitivity after perineural clonidine was associated with reduced hyperexcitability of DRG neurons. Rats underwent sham or PSNL surgery, followed 2 wk later by a single injection at the injury site of clonidine or saline. PSNL, but not sham surgery, reduced hindpaw mechanical withdrawal threshold, and clonidine, but not saline, partially reversed this effect 3 days after injection. Intracellular recording of neurons in whole DRG demonstrated similar changes in membrane properties and excitability in unaxotomized and axotomized neurons after PSNL compared with sham surgery, primarily depolarized resting membrane potential, reduced rheobase, presence of oscillations, and capability to fire repetitively. Most of these changes were present in small-, medium-, and large-diameter neurons. Perineural clonidine 3 days later significantly reversed many of these effects, whereas saline was without effect. We speculate that perineural clonidine reduces signals, likely proinflammatory cytokines and prostaglandins produced during Wallerian degeneration after nerve injury, which drive changes in ion channel expression in DRG somata leading to hyperexcitability and hypersensitivity.
周围神经损伤后的兴奋性增高发生在轴突切断的和相邻未轴突切断的背根神经节（DRG）神经元中，并导致超敏反应。以往的研究主要集中在近端神经损伤，尚未研究支配感觉测试部位的未轴突切断的神经元。本研究采用远端神经损伤（坐骨神经部分结扎[PSNL]），并使用荧光示踪剂鉴定支配超敏反应部位的轴突切断和未轴突切断的神经元。我们假设神经周围可乐定后超敏反应降低与DRG神经元兴奋性增高降低有关。大鼠接受假手术或PSNL手术，2周后在损伤部位单次注射可乐定或生理盐水。PSNL而非假手术降低了后爪机械性退缩阈值，注射后3天，可乐定而非生理盐水部分逆转了这种效应。对整个DRG中的神经元进行细胞内记录显示，与假手术相比，PSNL后未轴突切断和轴突切断的神经元在膜特性和兴奋性方面有类似变化，主要是静息膜电位去极化、基强度降低、存在振荡以及重复放电能力。这些变化大多出现在小、中、大直径神经元中。3天后神经周围注射可乐定显著逆转了其中许多效应，而生理盐水则无作用。我们推测神经周围可乐定减少了信号，可能是神经损伤后沃勒变性过程中产生的促炎细胞因子和前列腺素，这些信号驱动DRG胞体中离子通道表达的变化，导致兴奋性增高和超敏反应。
