Changes and Roles of Dorsal Root Ganglia in Nav1.7-related Congenital Insensitivity to Pain
10.11969/j.issn.1673-548X.2024.12.008
- VernacularTitle:背根神经节在Nav1.7相关先天性疼痛不敏感中的变化及作用
- Author:
Tingyu ZHAO
1
;
Ming PAN
;
Jinye SHI
Author Information
1. 200233 上海交通大学医学院附属第六人民医院麻醉科
- Publication Type:Journal Article
- Keywords:
Nav1.7;
Congenital insensitivity to pain;
Dorsal root ganglia;
Non-peptidergic neuron
- From:
Journal of Medical Research
2024;53(12):36-43
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes of dorsal root ganglia(DRG)neurons in rats with voltage-gated sodium channel 1.7 loss-of-function(Nav1.7 LOF)and its involvement in congenital insensitivity to pain.Methods Immunofluorescence,Western blot,and alternative splicing analysis were used to verify the expression deletion of DRG neurons and Nav1.7 in spinal cord of Nav1.7 LOF rats.Using antibodies for peripherin,calcitonin gene-related peptide(CGRP),isolectin B4(IB4),and neuronal nuclear antigen(NeuN)in the DRG and spinal cord tissues,immunofluorescence staining was performed to observe the differences in DRG neuronal sub-populations and central terminal projections between Nav1.7 LOF rats and wild-type rats.Bulk RNA-Seq and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the difference of gene expression in the DRG neurons between Nav1.7 LOF and WT rats.Following 55℃ thermal stimulation of the hind paw in Nav1.7 LOF rats,c-Fos and phospho-extracellular signal-regulated kinase(p-ERK)antibody staining was used to observe the activation of DRG neurons and spinal dorsal horn neurons.Results Nav1.7 was absent in the DRG neurons and spinal cord of Nav1.7 LOF rats.Compared with wild-type rats,Nav1.7 LOF rats exhibited a decreased proportion of IB4+non-peptidergic neurons in DRG tissues.Additionally,there was a significant loss of central projections of IB4+neurons in the spinal dorsal horn.The RNA-Seq and RT-qPCR results demonstrate that in Nav1.7 LOF rats,the gene expression of Mas-related G protein-coupled receptor(MRGPR),markers for 1B4+non-peptidergic neurons,was downregulat-ed.Compared with WT rats,there was no difference in c-Fos and p-ERK staining in DRG neurons of Nav1.7 LOF rats following ther-mal stimulation of the hindpaw.However,there was no c-Fos or p-ERK staining in spinal dorsal horn neurons,suggesting that the neu-rons were not activated.Conclusion Nav1.7 LOF rats exhibit a decreased proportion of IB4+non-peptideric neurons in DRG tissue and their central terminal projections.Noxious stimuli could activate DRG neurons,but could not activate dorsal horn neurons,suggesting the pain signal is interrupted between the central terminals of DRG neurons and the spinal dorsal horn.
