Department of Neurosurgery, XinHua Hospital (The Cranial Nerve Disease Center of Shanghai), Shanghai JiaoTong University School of Medicine , Shanghai , China.
Int J Neurosci. 2019 Oct;129(10):955-962. doi: 10.1080/00207454.2019.1595616. Epub 2019 Mar 31.
Despite the etiology of trigeminal neuralgia has been verified by microvascular decompression as vascular compression of the trigeminal root, very few researches concerning its underlying pathogenesis has been reported in the literature. The present study focused on those voltage-gated sodium channels, which are the structural basis for generation of ectopic action potentials. The trigeminal neuralgia modeling was obtained with infraorbital nerve chronic constriction injury (ION-CCI) in rats. Two weeks postoperatively, the infraorbital nerve (TN), the trigeminal ganglion (TG), and the brain stem (BS) were removed and analyzed with a series of molecular biological techniques. Western blot depicted a significant up-regulation of Nav1.3 in TN and TG but not in BS, while none of the other isoforms (Nav1.6, Nav1.7, Nav1.8, or Nav1.9) presented a statistical change. The Nav1.3 from ION-CCI group was quantified as 2.5-fold and 1.7-fold than that from sham group in TN and TG, respectively ( < .05). Immunocytochemistry showed the Nav1.3-IR from ION-CCI group accounted for 21.2 ± 2.3% versus 6.1 ± 1.2% from sham group in TN, while the Nav1.3-positive neurons from ION-CCI group accounted for 34.1 ± 3.5% versus 11.2 ± 1.8% from sham group in TG. Immunohistochemical labeling showed the Nav1.3 was co-localized with CGRP and IB4 but not with GFAP or NF-200 in TG. ION-CCI may give rise to an up-regulation of Nav1.3 in trigeminal nerve as well as in C-type neurons at the trigeminal ganglion. It implied that the ectopic action potential may generate from both the compressed site of the trigeminal nerve and the ganglion rather than from the trigeminal nuclei.
尽管三叉神经痛的病因已被微血管减压术证实为三叉神经根的血管压迫，但文献中很少有关于其潜在发病机制的报道。本研究集中于电压门控钠离子通道，该通道是产生异位动作电位的结构基础。通过在大鼠眶下神经慢性缩窄损伤（ION-CCI）中建立三叉神经痛模型。术后 2 周，取出眶下神经（TN）、三叉神经节（TG）和脑干（BS），并采用一系列分子生物学技术进行分析。Western blot 显示，TN 和 TG 中 Nav1.3 显著上调，但 BS 中无其他亚型（Nav1.6、Nav1.7、Nav1.8 或 Nav1.9）发生统计学变化。ION-CCI 组的 Nav1.3 比 sham 组分别增加了 2.5 倍和 1.7 倍（<0.05）。免疫细胞化学显示，ION-CCI 组的 Nav1.3-IR 占 TN 中 sham 组的 21.2±2.3%，而 ION-CCI 组的 Nav1.3 阳性神经元占 sham 组的 34.1±3.5%。免疫组织化学标记显示，Nav1.3 与 CGRP 和 IB4 共定位，但与 TG 中的 GFAP 或 NF-200 不共定位。ION-CCI 可能导致三叉神经和三叉神经节 C 型神经元中 Nav1.3 的上调。这表明异位动作电位可能源自三叉神经受压部位和神经节，而不是源自三叉神经核。
