Han Shoumeng, Chen Xin, Ma Li, Zeng Xin, Wang Ying, Xie Tingting, Wu Fancan, Song Kun, Hashimoto Kenji, Wang Hanbing, Wang Long
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Anesthesiology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Neurosci Bull. 2025 Aug 20. doi: 10.1007/s12264-025-01454-9.
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.
神经性疼痛是一种由神经系统损伤或功能障碍引起的慢性疾病。虽然脾脏可能影响神经性疼痛，但其作用一直未得到充分理解。本研究表明，在慢性缩窄性损伤（CCI）小鼠模型中，脾脏通过终纹床核（BNST）-下丘脑室旁核（PVN）神经回路在调节神经性疼痛中起关键作用。脾切除术、脾去神经支配或脾交感神经切除术显著提高了CCI小鼠的机械性撤离阈值（MWT），并减少了背根神经节（DRG）中的巨噬细胞浸润。将伪狂犬病病毒注射到脾脏中显示其与大脑中的BNST和PVN有连接。对BNST-PVN回路进行化学遗传学抑制会增加DRG中的巨噬细胞浸润并降低MWT；脾切除术、脾去神经支配或交感神经切除术可逆转这些作用。这些发现强调了受BNST-PVN回路调节的脾脏在神经性疼痛中的关键作用。
