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First\u2010line therapies, such as proton pump inhibitors and\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Helicobacter pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      eradication, often provide limited relief, prompting interest in alternative, mechanism\u2010based treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To review the literature on the use of predominantly central and predominantly peripheral neuromodulators in FD and GP and to develop a symptom\u2010directed therapeutic framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a comprehensive review of the literature, synthesizing data from randomized controlled trials, observational studies, and clinical guidelines. Pharmacological profiles, pathophysiological targets, and safety considerations were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Predominantly central neuromodulators, particularly tricyclic antidepressants (TCA) and mirtazapine, are effective in reducing visceral hypersensitivity and are most appropriate for epigastric pain syndrome (EPS). Predominantly peripheral neuromodulators\u2014including prokinetic agents such as metoclopramide, domperidone, levosulpiride, cinitapride, prucalopride, and itopride\u2014are beneficial in postprandial distress syndrome (PDS) and GP, especially for nausea and early satiation. Treatment selection should be individualized according to the predominant symptom profile, considering drug receptor specificity, safety, psychiatric comorbidities, and cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neuromodulators provide a rational, mechanism\u2010based treatment option for FD and GP, and a symptom\u2010oriented approach may optimize patient outcomes; although high\u2010quality, subtype\u2010specific trials are needed to strengthen the evidence base.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70278","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:32:19Z","timestamp":1772965939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Central and Peripheral Neuromodulators in Functional Dyspepsia and Gastroparesis: A Symptom\u2010Based Clinical Review"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-4744","authenticated-orcid":false,"given":"Ignacio","family":"Hanna\u2010Jairala","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology Hospital Alcivar  Guayaquil Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-6704","authenticated-orcid":false,"given":"Jan","family":"Tack","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Gastroenterology and Hepatology University Hospitals Leuven, KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8178-0453","authenticated-orcid":false,"given":"Douglas A.","family":"Drossman","sequence":"additional","affiliation":[{"name":"Center for Education and Practice of Biopsychosocial Care, Drossman Gastroenterology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.011"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.154"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102022\u2010327737"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16046"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14238"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16072"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30469\u20104"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.02.042"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.11.279"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002800"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14774"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.08.015"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.249"},{"issue":"2","key":"e_1_2_12_16_1","first-page":"106","article-title":"Brain Gut Microbiota Axis. 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