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...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.展开更多
基金supported by the National Natural Science Foundation of China(82201549)the Hubei Provincial Natural Science Foundation of China(220100579)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120050 and 2023A1515110107).
文摘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.
