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The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract


Review

. 2024 Nov 22.


doi: 10.1038/s41575-024-01017-9.


Online ahead of print.

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Review

Kimberly A Meerschaert et al.


Nat Rev Gastroenterol Hepatol.


.

Abstract

Visceral pain is a major clinical problem and one of the most common reasons patients with gastrointestinal disorders seek medical help. Peripheral sensory neurons that innervate the gut can detect noxious stimuli and send signals to the central nervous system that are perceived as pain. There is a bidirectional communication network between the gastrointestinal tract and the nervous system that mediates pain through the gut-brain axis. Sensory neurons detect mechanical and chemical stimuli within the intestinal tissues, and receive signals from immune cells, epithelial cells and the gut microbiota, which results in peripheral sensitization and visceral pain. This Review focuses on molecular communication between these non-neuronal cell types and neurons in visceral pain. These bidirectional interactions can be dysregulated during gastrointestinal diseases to exacerbate visceral pain. We outline the anatomical pathways involved in pain processing in the gut and how cell-cell communication is integrated into this gut-brain axis. Understanding how bidirectional communication between the gut and nervous system is altered during disease could provide new therapeutic targets for treating visceral pain.

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Conflict of interest statement

Competing interests: I.M.C. is on scientific advisory boards for GSK Pharmaceuticals and Nilo Therapeutics. He also consults for Panther Life Sciences and Fzata. His laboratory has received sponsored research support from GSK, Abbvie/Allergan and Moderna. K.A.M. declares no competing interests.

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