Upregulation of Nav1.6 expression in the ventral posterolateral nucleus of thalamus contributes to hyperalgesia in a model of Parkinson's disease

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-10-28 DOI:10.1016/j.expneurol.2024.115032

Zhiwei Li, Jiamin Luo, Chengjiyuan Li, Hongyan Zhu

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Abstract

Pain is the most common non-motor manifestation of Parkinson's disease (PD), affecting the quality of life for patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals. Here we investigated the expression patterns of Nav1.6 in the ventral posterolateral (VPL) nucleus of the thalamus and its involvement in the development of hyperalgesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. The results showed a significant increase in Nav1.6 expression in reactive astrocytes of the ipsilateral VPL in 6-OHDA-lesioned rats at 4 weeks post-injection. Moreover, 6-OHDA-lesioned rats exhibited mechanical hyperalgesia, but did not display thermal hyperalgesia in the ipsilateral paw at the same time point. The down-regulation of Nav1.6 in the ipsilateral VPL can reduce mechanical hyperalgesia and improve sensorimotor impairments in 6-OHDA- lesioned rats. Furthermore, the analysis of local field potentials (LFPs) revealed that the increased Nav1.6 may participate in abnormal synchronized oscillations within the thalamocortical loop in 6-OHDA-lesioned rats. These findings suggest that the altered expression of Nav1.6 in astrocytes of the VPL may play an important role in the abnormal processing of pain within the thalamocortical circuit, contributing to the formation of mechanical hyperalgesia in animal models of PD.

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丘脑腹侧后外侧核中 Nav1.6 表达的上调有助于帕金森病模型中的痛觉亢进

疼痛是帕金森病（PD）最常见的非运动表现，影响患者的生活质量。Nav1.6是成年哺乳动物大脑中最丰富的电压门控钠通道（VGSCs）亚型。在此，我们研究了 Nav1.6 在丘脑腹侧后外侧核（VPL）中的表达模式，以及它在 6-羟基多巴胺（6-OHDA）缺失大鼠痛觉亢进发展过程中的参与。结果显示，在注射后4周，6-OHDA缺失大鼠同侧VPL的反应性星形胶质细胞中Nav1.6的表达明显增加。此外，6-OHDA-lesioned 大鼠表现出机械痛觉减退，但在同一时间点，同侧爪子没有表现出热痛觉减退。下调同侧 VPL 中的 Nav1.6 可以减轻 6-OHDA 损伤大鼠的机械痛觉亢进并改善其感觉运动障碍。此外，对局部场电位（LFPs）的分析表明，Nav1.6 的增加可能参与了 6-OHDA 病损大鼠丘脑皮层环路内的异常同步振荡。这些研究结果表明，Nav1.6在VPL星形胶质细胞中的表达改变可能在丘脑皮质环路内疼痛的异常处理中发挥了重要作用，导致了帕金森病动物模型中机械性痛觉亢进的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.