Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders

Akinari Sawada, Mengyu Zhang, Ahsen Ustaoglu, Kornilia Nikaki, Chung Lee, Philip Woodland, Etsuro Yazaki, Shingo Takashima, Masaki Ominami, Fumio Tanaka, Clorinda Ciafardini, Fabio Nachman, Andrés Ditaranto, Joaquín Agotegaray, Claudio Bilder, Edoardo Savarino, C. Prakash Gyawali, Roberto Penagini, Yasuhiro Fujiwara, Daniel Sifrim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. Aims: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. Methods: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. Results: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = −0.567, p < 0.001) and distal oesophagus (ρ = −0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). Conclusions: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow.

Original languageEnglish
Pages (from-to)100-112
Number of pages13
JournalAlimentary Pharmacology and Therapeutics
Issue number1
StatePublished - Jan 2024


  • achalasia
  • chest pain
  • dysphagia
  • oesophageal motility disorders
  • oesophageal mucosal afferent nerves


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