Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

Zhang, Fu‐Chao; Wei, Ying‐Xue; Weng, Rui‐Xia; Xu, Qi‐Ya; Li, Rui; Yu, Yang; Xu, Guang‐Yin

doi:10.1111/cns.14534

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…Colorectal distention (CRD) is a well-established method for measuring visceral pain threshold. 53 During the procedure, mice were fully anesthetized with isoflurane. A special 1.5 cm flexible balloon was then inserted 2 cm into the anus and secured to the tail with pressure-sensitive tape to prevent slipping.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice

Yi,

Lu,

Zhu

et al. 2024

Mol Pain

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Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

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Section: Methodsmentioning

confidence: 99%

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice

Yi,

Lu,

Zhu

et al. 2024

Mol Pain

View full text Add to dashboard Cite

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A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing

Zhang,

Weng,

et al. 2024

Nat Commun

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Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

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Sinisan Alleviates Stress-Induced Intestinal Dysfunction and Depressive-like Behaviors in Mice with Irritable Bowel Syndrome by Enhancing the Intestinal Barrier and Modulating Central 5-Hydroxytryptamine

Zeng,

Jiang,

Yin

et al. 2024

IJMS

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Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice.

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Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

Cited by 3 publications

References 44 publications

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice

A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing

Sinisan Alleviates Stress-Induced Intestinal Dysfunction and Depressive-like Behaviors in Mice with Irritable Bowel Syndrome by Enhancing the Intestinal Barrier and Modulating Central 5-Hydroxytryptamine

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