{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:21:33Z","timestamp":1790857293983,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,5]],"date-time":"2015-04-05T00:00:00Z","timestamp":1428192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK074480"],"award-info":[{"award-number":["DK074480"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BioMed Martin co-funded by EU","award":["26220220187"],"award-info":[{"award-number":["26220220187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gastroesophageal reflux can cause high acidity in the esophagus and trigger heartburn and pain. However, because of the esophageal mucosal barrier, the acidity at the nerve terminals of pain\u2010mediating C\u2010fibers in esophageal mucosa is predicted to be substantially lower. We hypothesized that the esophageal dorsal root ganglia (<jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content>) C\u2010fibers are activated by mild acid (compared to acidic reflux), and express receptors and ion channels highly sensitive to acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Extracellular single unit recordings of activity originating in esophageal <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> C\u2010fiber nerve terminals were performed in the innervated esophagus preparation <jats:italic>ex vivo<\/jats:italic>. Acid was delivered in a manner that bypassed the esophageal mucosal barrier. The expression of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for selected receptors in esophagus\u2010specific <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> neurons was evaluated using single cell <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Mild acid (<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\u00a0=\u00a06.5\u20135.5) activated esophageal <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> C\u2010fibers in a <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\u2010dependent manner. The response to mild acid at <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\u00a0=\u00a06 was not affected by the <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 selective antagonist iodo\u2010resiniferatoxin. The majority (70\u201395%) of esophageal <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> C\u2010fiber neurons (<jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1\u2010positive) expressed <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for acid sensing ion channels (<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1a, <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1b, <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2b, and\/or <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>3), two\u2010pore\u2010domain (K2P) potassium channel <jats:styled-content style=\"fixed-case\">TASK<\/jats:styled-content>1, and the proton\u2010sensing G\u2010protein coupled receptor <jats:styled-content style=\"fixed-case\">OGR<\/jats:styled-content>1. Other evaluated targets (<jats:styled-content style=\"fixed-case\">PKD<\/jats:styled-content>2L1, <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">TASK<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">TALK<\/jats:styled-content>1, G2A, <jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>4, and <jats:styled-content style=\"fixed-case\">TDAG<\/jats:styled-content>8) were expressed rarely.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Guinea pig esophageal <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> C\u2010fibers are activated by mild acid via a <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1\u2010independent mechanism, and express <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for several receptors and ion channels highly sensitive to acid. The high acid sensitivity of esophageal C\u2010fibers may contribute to heartburn and pain in conditions of reduced mucosal barrier function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12561","type":"journal-article","created":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T04:03:14Z","timestamp":1428292994000},"page":"865-874","source":"Crossref","is-referenced-by-count":20,"title":["Acid sensitivity of the spinal dorsal root ganglia C\u2010fiber nociceptors innervating the guinea pig esophagus"],"prefix":"10.1111","volume":"27","author":[{"given":"F.","family":"Ru","sequence":"first","affiliation":[{"name":"Medicine The Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"P.","family":"Banovcin","sequence":"additional","affiliation":[{"name":"Pathophysiology and Gastroenterology Comenius University in Bratislava Jessenius Faculty of Medicine Martin 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