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Esophageal motility disorders represent mechanical dysfunctions that originate from abnormalities in neural control, underscoring the need to understand how neural and mechanical processes interact to produce coordinated motion. We present an empirically guided neuromechanical model of the esophagus, comprising unidirectionally coupled relaxation oscillators activated by intrinsic enteric nervous system mechanoreceptors sensitive to wall distension. The model reveals complex behaviors emerging from interactions among its components, predicting various clinically observed normal and abnormal esophageal responses to distension. Specifically, repetitive antegrade contractions (RACs) are shown to arise from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neural activities and mechanical input through these intrinsic distension-sensitive mechanoreceptors. When this balance is affected, contraction patterns resembling motility disorders emerge. For example, clinically observed repetitive retrograde contractions emerge due to hypersensitive mechanoreceptors in the esophageal wall. Such neuromechanical insights may ultimately guide the development of targeted pharmacological interventions.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013778","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T18:48:06Z","timestamp":1766774886000},"page":"e1013778","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modeling based insights into mechanical dysfunction in esophageal motility disorders"],"prefix":"10.1371","volume":"21","author":[{"given":"Guy","family":"Elisha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Halder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-4092","authenticated-orcid":true,"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin A.","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Kahrilas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Pandolfino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0665-3454","authenticated-orcid":true,"given":"Neelesh A.","family":"Patankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"issue":"4","key":"pcbi.1013778.ref001","doi-asserted-by":"crossref","DOI":"10.1172\/JCI143771","article-title":"Gastrointestinal motility disorders in neurologic disease","volume":"131","author":"M Camilleri","year":"2021","journal-title":"J Clin Invest."},{"issue":"8","key":"pcbi.1013778.ref002","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.14870","article-title":"Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction","volume":"37","author":"JR Jamka","year":"2025","journal-title":"Neurogastroenterol Motil."},{"issue":"9","key":"pcbi.1013778.ref003","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrgastro.2016.107","article-title":"The bowel and beyond: the enteric nervous system in neurological disorders","volume":"13","author":"M Rao","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol."},{"issue":"9","key":"pcbi.1013778.ref004","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/BF01303162","article-title":"U.S. householder survey of functional gastrointestinal disorders. 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