The Bed Nucleus of the Stria Terminalis-Paraventricular Nucleus of the Hypothalamus Neural Circuit Regulates Neuropathic Pain Through the Brain-Spleen Axis.
10.1007/s12264-025-01454-9
- Author:
Shoumeng HAN
1
;
Xin CHEN
2
;
Li MA
3
;
Xin ZENG
1
;
Ying WANG
1
;
Tingting XIE
3
;
Fancan WU
3
;
Kun SONG
3
;
Kenji HASHIMOTO
4
;
Hanbing WANG
5
,
6
;
Long WANG
6
,
7
Author Information
1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
2. Department of Anesthesiology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
3. Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, China.
4. Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan. hashimoto@faculty.chiba-u.jp.
5. Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, China. fswhbing@
6. com.
7. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. wanglongwhu@
- Publication Type:Journal Article
- Keywords:
Brain-Spleen axis;
Neuropathic pain;
Splenectomy;
Splenic denervation;
Splenic sympathectomy
- MeSH:
Animals;
Neuralgia/pathology*;
Septal Nuclei/physiopathology*;
Male;
Spleen/physiopathology*;
Paraventricular Hypothalamic Nucleus/physiopathology*;
Mice, Inbred C57BL;
Splenectomy;
Mice;
Neural Pathways/physiopathology*;
Disease Models, Animal;
Ganglia, Spinal/physiopathology*;
Sympathectomy;
Macrophages
- From:
Neuroscience Bulletin
2025;41(12):2148-2166
- CountryChina
- Language:English
-
Abstract:
Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
