Shoumeng Han1  · Xin Chen2  · Li Ma3  · Xin Zeng1  · Ying Wang1  · Tingting Xie3  · Fancan Wu3  · Kun Song3  · Kenji Hashimoto4  · Hanbing Wang3  · Long Wang1

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

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.

Keywords

Brain-Spleen axis； Neuropathic pain； Splenectomy； Splenic denervation； Splenic sympathectomy

[SpringerLink]