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

• Published in: CNS neuroscience & therapeutics Vol. 30; no. 4; pp. e14534 - n/a
• Main Authors: Zhang, Fu‐Chao, Wei, Ying‐Xue, Weng, Rui‐Xia, Xu, Qi‐Ya, Li, Rui, Yu, Yang, Xu, Guang‐Yin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc
• Subjects: Abdomen; Animals; Antibodies; Brain research; c-Fos protein; Catheters; Central nervous system; Colorectal Neoplasms; Consciousness; Cortex (insular); Distension; Electromyography; Females; glutamatergic neurons; Inflammation; Insular Cortex; Irritable bowel syndrome; Irritable Bowel Syndrome - metabolism; Laboratory animals; Mice; Neonates; Nervous system; neural circuit; Original; Pain; paraventricular thalamus; Photometry; Physiology; Thalamus; visceral pain; Visceral Pain - metabolism; neural circuit; visceral pain; insular cortex; paraventricular thalamus; irritable bowel syndrome; glutamatergic neurons
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.14534

Aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, but its pathogenesis remains incompletely understood, particularly the involvements of central nervous system sensitization in colorectal visceral pain. Our study was to investigate whether the paraventricular thalamus (PVT) projected to the insular cortex (IC) to regulate colorectal visceral pain in neonatal colonic inflammation (NCI) mice and underlying mechanisms. Methods We applied optogenetic, chemogenetic, or pharmacological approaches to manipulate the glutamatergicPVT‐IC pathway. Fiber photometry was used to assess neuronal activity. Electromyography activities in response to colorectal distension (CRD) were measured to evaluate the colorectal visceral pain. Results NCI enhanced c‐Fos expression and calcium activity upon CRD in the ICGlu, and optogenetic manipulation of them altered colorectal visceral pain responses accordingly. Viral tracing indicated that the PVTGlu projected to the ICGlu. Optogenetic manipulation of PVTGlu changed colorectal visceral pain responses. Furthermore, selective optogenetic modulation of PVT projections in the IC influenced colorectal visceral pain, which was reversed by chemogenetic manipulation of downstream ICGlu. Conclusions This study identified a novel PVT‐IC neural circuit playing a critical role in colorectal visceral pain in a mouse model of IBS. A direct PVT‐IC glutamate neural circuit playing a critical role in visceral hypersensitivity in a mouse model of IBS. This work will strengthen fundamental research on the involvement of central nervous system in visceral hyperalgesia and provide potential therapeutic targets toward effective treatment.