Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6 Alan Edwards Center for Research on Pain, McGill University, Montreal, Quebec, Canada H3A 2B2 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 2B2.
Pain. 2011 Jul;152(7):1502-1510. doi: 10.1016/j.pain.2011.02.035. Epub 2011 Mar 12.
Trigeminal neuropathic pain is associated with trigeminal nerve damage. Significant remodeling of the peripheral nervous system may contribute to the pain; however, the changes and the factors that drive them have not been well described. In this study, a partial injury of the mental nerve of the rat, a purely sensory branch of the trigeminal nerve, resulted in prolonged mechanical allodynia in the lower lip skin persisting up to 4 months. Although nonpeptidergic, P2X3-immunoreactive (IR) C fibers displayed a transient decrease in density of innervation in the skin; they returned to sham levels by 4 weeks after lesioning. Ectopic sympathetic (as detected by anti-dopamine-β-hydroxylase antibodies) and parasympathetic (as detected by antibodies against the vesicular acetylcholine transporter) fibers in the upper dermis were apparent early on the following lesion (2 weeks), in close apposition with regenerating nonpeptidergic fibers. Meanwhile, the glial cell line-derived growth factor (GDNF) showed a quick upregulation in the skin after nerve lesioning, with levels peaking at 4 weeks. This suggests that an excess of GDNF in the skin drives the nonpeptidergic C-fiber regeneration and parasympathetic fiber sprouting in the upper dermis, and could be an important mechanism in trigeminal neuropathic pain. This article provides an in-depth description of the changes in nonpeptidergic fibers in the skin after nerve lesioning, and measures, for the first time, GDNF protein levels in the skin after a nerve lesion, providing strong evidence for the role of GDNF in modulating innervation of the nonpeptidergic and parasympathetic fibers in the skin after injury.
三叉神经病理性疼痛与三叉神经损伤有关。外周神经系统的显著重塑可能导致疼痛；然而，这些变化及其驱动因素尚未得到很好的描述。在这项研究中，大鼠颏神经（三叉神经的纯感觉分支）的部分损伤导致下唇皮肤的机械性超敏持续长达 4 个月。尽管是非肽能的，P2X3 免疫反应性（IR）C 纤维在皮肤中的支配密度短暂下降；它们在损伤后 4 周恢复到假手术水平。真皮上层异位交感神经（通过抗多巴胺-β-羟化酶抗体检测到）和副交感神经（通过针对囊泡乙酰胆碱转运蛋白的抗体检测到）纤维在损伤后早期（2 周）就很明显，与再生的非肽能纤维紧密相邻。同时，胶质细胞系衍生的神经营养因子（GDNF）在神经损伤后皮肤中迅速上调，在 4 周时达到峰值。这表明皮肤中 GDNF 过多会驱动非肽能 C 纤维再生和真皮上层副交感神经纤维的发芽，并且可能是三叉神经病理性疼痛的重要机制。本文深入描述了神经损伤后皮肤中非肽能纤维的变化，并首次测量了神经损伤后皮肤中的 GDNF 蛋白水平，为 GDNF 在调节损伤后皮肤中非肽能和副交感神经纤维支配中的作用提供了有力证据。
