Chronic environmental cold stress increases migraine susceptibility associated with regional dysregulation of RBFOX1 and PTPRD in the somatosensory network
6 affiliations
- 1Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- 2Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
- 3Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
- 4Third Clinical Medical College of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
- 5Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- 6China National Clinical Research Center for Neurological Diseases, Beijing, China
Abstract
IntroductionEnvironmental stressors influence migraine chronification, yet mechanisms linking chronic cold exposure to central sensitization remain unclear.MethodsUtilizing a Mendelian randomization framework, we identified genetic associations between occupational cold exposure and increased migraine susceptibility, prioritizing gut microbiota and functional somatosensory brain imaging phenotypes as potential mediators. To explore these in silico predictions in a parallel in vivo context, we evaluated a mouse model subjected to combined physical cold stress and an acute nitroglycerin (NTG) trigger.ResultsBehaviorally, this dual exposure exacerbated migraine-like mechanical allodynia and spontaneous pain compared to NTG alone. Morphological and molecular analyses revealed significant upregulation of the pain-related neuropeptide CGRP in the trigeminocervical complex of cold-stressed mice. Furthermore, immunofluorescence and biochemical expression profiling demonstrated a selective regional depletion of the RNA-splicing factor RBFOX1 and a distinct overexpression of the synaptic receptor PTPRD within the examined brain parenchyma across the somatosensory network.DiscussionCollectively, these translational observations suggest that environmental cold stress alters the regional molecular baseline of sensory networks, potentially lowering the neurological threshold for migraine and highlighting RBFOX1 and PTPRD as specific neurobiological signatures of this susceptibility.
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BibTeX
@article{wang2026chronic,
title = {{Chronic environmental cold stress increases migraine susceptibility associated with regional dysregulation of RBFOX1 and PTPRD in the somatosensory network}},
author = {Yaolou Wang and Jinru Shen and Yingjie Shen and Binbin Gui and Yansong Liu and Wei Zhang and Liuyu Xu and Liang Liu and Qifan Zhang and Aihua Liu and Aihua Liu and Aihua Liu and Aihua Liu},
journal = {Frontiers in Neurology},
year = {2026},
month = nov,
doi = {10.3389/fneur.2026.1965355},
url = {https://doi.org/10.3389/fneur.2026.1965355},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chronic environmental cold stress increases migraine susceptibility associated with regional dysregulation of RBFOX1 and PTPRD in the somatosensory network
AU - Yaolou Wang
AU - Jinru Shen
AU - Yingjie Shen
AU - Binbin Gui
AU - Yansong Liu
AU - Wei Zhang
AU - Liuyu Xu
AU - Liang Liu
AU - Qifan Zhang
AU - Aihua Liu
AU - Aihua Liu
AU - Aihua Liu
AU - Aihua Liu
PY - 2026
DA - 2026/11/05
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1965355
UR - https://doi.org/10.3389/fneur.2026.1965355
AB - IntroductionEnvironmental stressors influence migraine chronification, yet mechanisms linking chronic cold exposure to central sensitization remain unclear.MethodsUtilizing a Mendelian randomization framework, we identified genetic associations between occupational cold exposure and increased migraine susceptibility, prioritizing gut microbiota and functional somatosensory brain imaging phenotypes as potential mediators. To explore these in silico predictions in a parallel in vivo context, we evaluated a mouse model subjected to combined physical cold stress and an acute nitroglycerin (NTG) trigger.ResultsBehaviorally, this dual exposure exacerbated migraine-like mechanical allodynia and spontaneous pain compared to NTG alone. Morphological and molecular analyses revealed significant upregulation of the pain-related neuropeptide CGRP in the trigeminocervical complex of cold-stressed mice. Furthermore, immunofluorescence and biochemical expression profiling demonstrated a selective regional depletion of the RNA-splicing factor RBFOX1 and a distinct overexpression of the synaptic receptor PTPRD within the examined brain parenchyma across the somatosensory network.DiscussionCollectively, these translational observations suggest that environmental cold stress alters the regional molecular baseline of sensory networks, potentially lowering the neurological threshold for migraine and highlighting RBFOX1 and PTPRD as specific neurobiological signatures of this susceptibility.
SN - 1664-2295
ER -