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

Abstract 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 glutamatergic PVT‐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 IC Glu , and optogenetic manipulation of them altered colorectal visceral pain responses accordingly. Viral tracing indicated that the PVT Glu projected to the IC Glu . Optogenetic manipulation of PVT Glu 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 IC Glu . Conclusions This study identified a novel PVT‐IC neural circuit playing a critical role in colorectal visceral pain in a mouse model of IBS.