Dataset Information

The Bed Nucleus of the Stria Terminalis-Paraventricular Nucleus of the Hypothalamus Neural Circuit Regulates Neuropathic Pain Through the Brain-Spleen Axis.

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.

SUBMITTER: Han S

PROVIDER: S-EPMC12698908 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature

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The Bed Nucleus of the Stria Terminalis-Paraventricular Nucleus of the Hypothalamus Neural Circuit Regulates Neuropathic Pain Through the Brain-Spleen Axis.

Han Shoumeng S Chen Xin X Ma Li L Zeng Xin X Wang Ying Y Xie Tingting T Wu Fancan F Song Kun K Hashimoto Kenji K Wang Hanbing H Wang Long L

Neuroscience bulletin 20250820 12

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 sympathe ...[more]

PMID: 40835804

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Project description:To identify genes that are downstream of gonadal hormones and that control dimorphic behaviors, we used a MEEBO array platform to profile gene expression of adult male and female hypothalamus against a whole brain reference sample. The experimental design allowed us to identify genes that are upreguated in the hypothalamus compared to the whole brain and are dimorphically expressed between the two sexes. In situ hybridization of candiate genes were carried out to validate the dimorphic expression of these genes in the hypothalamus. Array results were used to create a list of genes to screen by in situ hybridization. For each normalization method, a list of genes that were upregulated in the male or the female was created, and a gene had to be on a set number of these individual normalization lists in order to be considered for screening. A similar method was used to create a list of hypothalamic upregulated genes. The final screening list was comprised of genes that were upregulated in the male or female as well as in the hypothalamus. If in situ hybridization proved that the gene was upregulated in the male or female brain, we concluded that that transcript was differentially expressed. No one normalization method was weighted over another, and the array results were used to create a screening list for in situ hybridizations. Hypothalami from 4 adult animals of each sex were microdissected and pooled for each experimental sample and the whole brain plus pituitary from one male and one female were pooled to provide the reference sample. Each set of samples (male and female) was hybridized to two arrays to provide two technical replicates for each set of samples taken. A total of three sets of samples were taken (three biological replicates). For the "_amp" Samples, source (hypothalamus and whole brain) mRNA was amplified using T7 based method. For this set, data were not normalized, rather the raw intensities were used to calculate ratios. Candidate genes from this study was also included in final list in situ screening.

Dataset Information

The Bed Nucleus of the Stria Terminalis-Paraventricular Nucleus of the Hypothalamus Neural Circuit Regulates Neuropathic Pain Through the Brain-Spleen Axis.

Publications

The Bed Nucleus of the Stria Terminalis-Paraventricular Nucleus of the Hypothalamus Neural Circuit Regulates Neuropathic Pain Through the Brain-Spleen Axis.

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