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dc.contributor.authorUstaoglu, A
dc.contributor.authorSawada, A
dc.contributor.authorLee, C
dc.contributor.authorLei, W-Y
dc.contributor.authorChen, C-L
dc.contributor.authorHackett, R
dc.contributor.authorSifrim, D
dc.contributor.authorPeiris, M
dc.contributor.authorWoodland, P
dc.date.accessioned2021-03-23T11:58:26Z
dc.date.available2021-03-23T11:58:26Z
dc.date.issued2021-03-03
dc.identifier.urihttps://qmro.qmul.ac.uk/xmlui/handle/123456789/70820
dc.description.abstractThe underlying causes of heartburn, characteristic symptom of gastro-esophageal reflux disease(GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease(NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1(TRPV1), transient receptor potential Melastatin 8(TRPM8), and acid sensing ion channel 3(ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterised TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of GERD patients. We studied 10 NERD, 10 erosive reflux disease(ERD), 7 functional heartburn(FH), and 8 Barrett's esophagus(BE) patients. Biopsies obtained from the distal esophageal mucosa were co-stained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. NERD patients had significantly increased expression of TRPV1 on superficial sensory nerves compared to ERD (p=0.028) or BE (p=0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in NERD and ERD patients (p=<0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localisation of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 co-expression on epithelial cells in NERD and ERD suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in NERD patients, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.en_US
dc.languageeng
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
dc.subjectTRPV1en_US
dc.subjectnon erosive reflux diseaseen_US
dc.subjectrefluxen_US
dc.titleHeartburn Sensation in Non-Erosive Reflux Disease: Pattern of Superficial Sensory Nerves Expressing TRPV1 and Epithelial Cells Expressing ASIC3 Receptors.en_US
dc.typeArticleen_US
dc.identifier.doi10.1152/ajpgi.00013.2021
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/33655767en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
pubs.publisher-urlhttps://doi.org/10.1152/ajpgi.00013.2021
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US


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