{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:41:56Z","timestamp":1785519716299,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T00:00:00Z","timestamp":1383523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010erosive reflux disease (<jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content>) patients generally present with heartburn as the main symptom. Antidepressants might help to relieve heartburn by acting on the esophagus\u2010brain axis. We aimed to assess the effect of nortriptyline on behavioral and brain responses to painful esophageal acid infusion in <jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content> patients evaluated with functional magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a randomized double\u2010blind crossover design, 20 <jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content> patients off proton pump inhibitors (36.1\u00a0\u00b1\u00a09.3\u00a0years, 75% women) were assigned to 21\u00a0days of nortriptyline and placebo, in counterbalanced order, with a 21\u00a0days washout period in between both treatment periods. Changes in acid\u2010induced brain response on <jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content> and heartburn perception were assessed and at the end of each treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Nortriptyline significantly reduced the acid\u2010induced brain response in prefrontal cortex (median [<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content>]: \u22121.9 [\u22124.5 to \u22120.1] vs \u22120.3 [\u22122.5 to 2.3]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.050), caudate (\u22123.0 [\u22125.1 to \u22120.01] <jats:italic>vs<\/jats:italic> 0.48 [\u22121.9 to 3.1]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.029), insula (\u22122.4 [\u22124.8 to \u22120.6] <jats:italic>vs<\/jats:italic> \u22120.2 [\u22121.5 to 1.5]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.029), cingulate (\u22124.2 [\u22128.8 to \u22120.1] <jats:italic>vs<\/jats:italic> \u22120.6 [\u22121.8 to 3.0]; p\u00a0=\u00a00.017), and hippocampus (\u22122.7 [\u22126.0 to 0.5] <jats:italic>vs<\/jats:italic> \u22120.04 [\u22122.3 to 1.9]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.006) in comparison with placebo. However, there was no significant difference between nortriptyline and placebo in clinical outcomes and side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Nortriptyline decreased the brain response to esophageal acid infusion more markedly than placebo, but without clinical significance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12251","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T01:28:57Z","timestamp":1383614937000},"page":"187-195","source":"Crossref","is-referenced-by-count":27,"title":["Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non\u2010erosive reflux disease"],"prefix":"10.1111","volume":"26","author":[{"given":"C. M.","family":"Forcelini","sequence":"first","affiliation":[{"name":"Faculdade de Medicina Universidade de Passo Fundo (UPF) Passo Fundo Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o: Ci\u00eancias em Gastroenterologia e Hepatologia Faculdade de Medicina Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"J. C.","family":"Tomiozzo","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Universidade de Passo Fundo (UPF) Passo Fundo Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o: Ci\u00eancias em Gastroenterologia e Hepatologia Faculdade de Medicina Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Farr\u00e9","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID) Department of Clinical and Experimental Medicine University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Van Oudenhove","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID) Department of Clinical and Experimental Medicine University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Callegari\u2010Jacques","sequence":"additional","affiliation":[{"name":"Departamento de Estat\u00edstica UFRGS Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o: Ci\u00eancias em Gastroenterologia e Hepatologia Faculdade de Medicina Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil"},{"name":"Cl\u00ednica Kozma Passo Fundo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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