{"doi":"10.3390/cells14151146","title":"Molecular Mechanisms and Pathways in Visceral Pain","abstract":"<jats:p>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.</jats:p>","journal":"Cells","year":2025,"id":634960,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1647078,"name":"George Nicholas Verne","orcid":null,"position":1,"is_corresponding":false},{"id":1647077,"name":"Qiqi Zhou","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Molecular Mechanisms and Pathways in Visceral Pain","abstract":"<jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40801578","pmcid":"PMC12345894","openalex_id":"https://openalex.org/W4412711567","authors":[],"funders":[{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","grant_id":"DK099052","title":null},{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","grant_id":"DK118959","title":null},{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","grant_id":"CX001477","title":null},{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","grant_id":"CX002910","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK118959","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK099052","title":null},{"funder_name":"CSRD VA","grant_id":"I01 CX001477","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01DK099052-05","title":"Mechanisms of Altered Gastrointestinal Dysfunction"}],"total_grants":8,"fwci":11.6307,"citation_percentile":0.98848348,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":9}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/14/15/1146/pdf?version=1753431685","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/14/15/1146/pdf?version=1753431685","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/14/15/1146/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells14151146","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40801578","host_type":"repository"},{"url":"https://doaj.org/article/60b5aaf1217447f6a4acb1538d3bfac4","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12345894","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12345894","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12345894?pdf=render","host_type":"Europe_PMC"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12345894/","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/40801578/","host_type":""}],"fields_of_study":["Gastrointestinal motility and disorders","Ion Channels and Receptors","Pain Mechanisms and Treatments","Humans","Visceral Pain","Animals","Irritable Bowel Syndrome","TRPV Cation Channels","Acid Sensing Ion Channels","Signal Transduction"],"mesh_terms":["Animals","Humans","Signal Transduction","Irritable Bowel Syndrome","TRPV Cation Channels","Visceral Pain","Acid Sensing Ion Channels"],"keywords":["Visceral pain","Irritable bowel syndrome","Sensitization","TRPV1","Medicine","Chronic pain","Nociceptor","Pelvic pain","Bioinformatics","Transient receptor potential channel","Neuroscience","Interstitial cystitis","Fibromyalgia","Nociception","Internal medicine","Immunology","Receptor","Biology","Physical therapy","ncRNA","Visceral hypersensitivity","Disorders Of Gut–brain Interaction","Acid Sensing Ion Channels","Humans","Animals","TRPV Cation Channels","Review","Signal Transduction"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:25:51.658528Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}