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

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.