{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T10:14:42Z","timestamp":1756894482939,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,20]],"date-time":"2019-01-20T00:00:00Z","timestamp":1547942400000},"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":["DK110366"],"award-info":[{"award-number":["DK110366"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Acid reflux in the esophagus can induce painful sensations such as heartburn and non\u2010cardiac chest pain. These nociceptive symptoms are initiated by activation of <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1\u2010positive afferent C fibers in the esophagus. The present study aimed to explore a novel C fiber inhibition approach. We hypothesized that activation of <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 by acid enabled <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314, a membrane impermeable sodium channel blocker, to inhibit acid\u2010induced activation of esophageal nociceptive C fiber neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We determined the inhibitory effect of <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 in the presence of acid in guinea pig esophageal nociceptive vagal jugular C fiber neurons by both patch clamp recording in neuron soma and by extra\u2010cellular recording at nerve terminals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Our data demonstrated <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 alone did not inhibit sodium currents. However, when applied along with capsaicin to activate <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 was able to block sodium currents in esophageal\u2010specific jugular C fiber neurons. We then showed that in the presence of acid, <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 significantly blocked acid\u2010evoked activation of jugular C fiber neurons. This effect was attenuated by <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 antagonist <jats:styled-content style=\"fixed-case\">AMG<\/jats:styled-content>9810, suggesting acid\u2010mediated inhibitory effect of <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 was <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1\u2010dependent. Finally, we provided evidence at nerve endings that acid\u2010evoked action potential discharges in esophageal jugular C fibers were inhibited by <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 when applied in the presence of acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Inferences<\/jats:title><jats:p>Our data demonstrated that activation of <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 by acid enabled membrane impermeable sodium channel blocker <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 to inhibit acid\u2010induced activation in esophageal nociceptive C fibers. This supports a localized application of <jats:styled-content style=\"fixed-case\">QX<\/jats:styled-content>\u2010314 in the esophagus to block esophageal nociception in acid reflux disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13543","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T02:43:27Z","timestamp":1548038607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>QX<\/scp>\u2010314 inhibits acid\u2010induced activation of esophageal nociceptive C fiber neurons"],"prefix":"10.1111","volume":"31","author":[{"given":"Youtian","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1766-8774","authenticated-orcid":false,"given":"Shaoyong","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2013.06.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980824)398:2<289::AID-CNE9>3.0.CO;2-X"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.907bd.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00785.2001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12180"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.079574"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.05.020"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12561"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.487"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00142.2013"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00156.2014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00388.2007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.03.040"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5150-09.2010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(78)85403-4"},{"issue":"3","key":"e_1_2_9_19_1","first-page":"476","article-title":"Effects of local anesthetic QX\u2010314 on the membrane properties of hippocampal pyramidal neurons","volume":"220","author":"Connors BW","year":"1982","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06191"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.06.007"},{"volume-title":"Propagated Signaling: The Action Potential. 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