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Molecular Mechanisms and Pathways in Visceral Pain

Zhou, Qiqi, Verne, George Nicholas·2025·Cells
DOI 10.3390/cells14151146
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Abstract

Chronic visceral pain, a significant contributor to morbidity in the United States, affects millions and results in substantial economic costs. Despite its impact, the mechanisms underlying disorders of gut–brain interaction (DGBIs), such as irritable bowel syndrome (IBS), remain poorly understood. Visceral hypersensitivity, a hallmark of chronic visceral pain, involves an enhanced pain response in internal organs to normal stimuli. Various factors like inflammation, intestinal hyperpermeability, and epigenetic modifications influence its presentation. Emerging evidence suggests that persistent colonic stimuli, disrupted gut barriers, and altered non-coding RNA (ncRNA) expression contribute to the pathophysiology of visceral pain. Additionally, cross-sensitization of afferent pathways shared by pelvic organs underpins the overlap of chronic pelvic pain disorders, such as interstitial cystitis and IBS. Central sensitization and viscerosomatic convergence further exacerbate pain, with evidence showing IBS patients exhibit hypersensitivity to both visceral and somatic stimuli. The molecular mechanisms of visceral pain involve critical mediators such as cytokines, prostaglandins, and neuropeptides, alongside ion channels like transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channels (ASICs). These molecular insights indicate potential therapeutic targets and highlight the possible use of TRPV1 antagonists and ASIC inhibitors to mitigate visceral pain. This review explores the neurophysiological pathways of visceral pain, focusing on peripheral and central sensitization mechanisms, to advance the development of targeted treatments for chronic pain syndromes, particularly IBS and related disorders.

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Metadata

Authors
Zhou, Q., & Verne, G. N.
Venue
Cells
Publisher
MDPI AG
Published
2025-07-25
Volume
14
Issue
15
Pages
1146
ISSN
2073-4409
DOI
10.3390/cells14151146
Cited by
15
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK099052, DK118959, CX001477, CX002910)
  • Department of Veterans Affairs (DK099052, DK118959, CX001477, CX002910)

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Zhou, Q., & Verne, G. N. (2025). Molecular Mechanisms and Pathways in Visceral Pain. Cells. https://doi.org/10.3390/cells14151146

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