Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease

Woodland, Philip; Ooi, Joanne L.; Grassi, Federica; Nikaki, Kornilia; Lee, Chung; Evans, James A.; Koukias, Nikolaos; Triantos, Christos; McDonald, Stuart; Peiris, Madusha; Aktar, Rubina; Blackshaw, L. Ashley; Sifrim, Daniel

doi:10.1053/j.gastro.2017.07.017

Cited by 74 publications

(73 citation statements)

References 39 publications

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“…The historical cohorts were used for comparison . HV comprised 10 patients with a mean age of 24 years (range: 21‐42 years), NERD (normal endoscopic appearances and increased esophageal acid exposure, ie, “true” NERD): 13 patients, seven male, with a mean age of 50 years (range: 28‐75 years).…”

Section: Resultsmentioning

confidence: 99%

“…Biopsies were analyzed alongside other samples from patients with gastro‐esophageal reflux disease (GERD) by a research team member who was blinded as to which were from FH patients. Biopsy processing was exactly as previously described . After orientation, biopsies were fixed in 4% paraformaldehyde for 3 hours, followed by cryoprotection in 30% sucrose in phosphate‐buffered saline (PBS) for 24 hours at 0.4°C.…”

Section: Methodsmentioning

confidence: 99%

“…The position of each visualized nerve fiber relative to the esophageal lumen was recorded as previously described in our previous studies . For each 10‐mm section, the number of cell layers from the fiber to the luminal surface was noted and the results from all sections for each biopsy were compiled and a median value calculated.…”

Section: Methodsmentioning

confidence: 99%

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Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non‐erosive reflux disease patients

Nikaki

Woodland

Lee³

et al. 2019

Neurogastroenterology Motil

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Background Mucosal innervation in non‐erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux‐symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV. Methods Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP‐positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD. Results Eleven patients were included in the FH group with a mean age of 46 years (range 33‐69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4‐28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5). Conclusions The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non‐erosive reflux disease patients

Nikaki

Woodland

Lee³

et al. 2019

Neurogastroenterology Motil

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“…Although dysphagia may be associated with neurologic impairment and anatomic diseases that can affect these swallowing stages, the symptom may also result from esophageal hypersensitivity and/or hypervigilance, without any alteration in the oral, pharyngeal or esophageal transit (9,26) . In patients with non-erosive GERD, proximal and distal esophageal mucosa have more superficial afferent nerves compared with no reflux disease or patients with erosive disease and patients with Barrett esophagus (27) . Patients with extra esophageal manifestations of gastroesophageal reflux frequently have non-erosive disease in esophagus (15) , with the possibility to have more superficial afferent nerves and hypersensitivity in proximal esophageal body, explaining the possibility of dysphagia in these patients.…”

Section: Discussionmentioning

confidence: 97%

Swallowing in Patients With Laryngitis

Moda

Ricz

Aguiar-Ricz

et al. 2018

Arq. Gastroenterol.

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-Background -Dysphagia is described as a complaint in 32% of patients with laryngitis. Objective -The objective of this investigation was to evaluate oral and pharyngeal transit of patients with laryngitis, with the hypothesis that alteration in oral-pharyngeal bolus transit may be involved with dysphagia. Methods -Videofluoroscopic evaluation of the swallowing of liquid, paste and solid boluses was performed in 21 patients with laryngitis, 10 of them with dysphagia, and 21 normal volunteers of the same age and sex. Two swallows of 5 mL liquid bolus, two swallows of 5 mL paste bolus and two swallows of a solid bolus were evaluated in a random sequence. The liquid bolus was 100% liquid barium sulfate and the paste bolus was prepared with 50 mL of liquid barium and 4 g of food thickener (starch and maltodextrin). The solid bolus was a soft 2.2 g cookie coated with liquid barium. Durations of oral preparation, oral transit, pharyngeal transit, pharyngeal clearance, upper esophageal sphincter opening, hyoid movement and oral-pharyngeal transit were measured. All patients performed 24-hour distal esophageal pH evaluation previous to videofluoroscopy.Results -The evaluation of 24-hour distal esophageal pH showed abnormal gastroesophageal acid reflux in 10 patients. Patients showed longer oral preparation for paste bolus and a faster oral transit time for solid bolus than normal volunteers. Patients with laryngitis and dysphagia had longer preparation for paste and solid boluses, and a faster oral transit time with liquid, paste and solid boluses. Conclusion -A longer oral preparation for paste and solid boluses and a faster transit through the mouth are associated with dysphagia in patients with laryngitis.

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“…It has been suggested that TRPV1 receptors are expressed in afferent neuronal fibers, as observed in biopsies of patients with NERD, and in non‐neuronal cells, such as esophageal epithelial cells . A recent study demonstrated CGRP‐positive nerves close to the esophageal lumen in patients with NERD, which colocalized with TRPV1‐immunoreactive nerve fibers in mouse esophagus . Thus, further investigations are necessary.…”

Section: Discussionmentioning

confidence: 99%

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

Silva

Bingana

Sales

et al. 2018

Neurogastroenterology Motil

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Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease

Cited by 74 publications

References 39 publications

Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non‐erosive reflux disease patients

Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non‐erosive reflux disease patients

Swallowing in Patients With Laryngitis

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

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