Objective Little is known about the mucosal phenotype of the proximal human esophagus. There is evidence to suggest that the proximal esophagus is more sensitive to chemical and mechanical stimulation compared to the distal. This may have physiological relevance (e.g. in prevention of aspiration of gastroesophageal refluxate), but also pathological relevance (e.g. in reflux perception or dysphagia). Reasons for this increased sensitivity are unclear but may include impairment in mucosal barrier integrity or changes in sensory innervation. We assessed mucosal barrier integrity and afferent nerve distribution in the proximal and distal esophagus of healthy human volunteers. Design In 10 healthy volunteers baseline proximal and distal esophageal impedance was measured in vivo. Esophageal mucosal biopsies from the distal and proximal esophagus were taken and baseline transepithelial electrical resistance (TER) was measured in Ussing chambers. Biopsies were examined immunohistochemically for presence and location of calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers. Results Baseline impedance was higher in the proximal than in the distal esophagus (2936Ω(SD578) vs. 2229Ω(SD821); p = 0.03), however, baseline TER was not significantly different between them. Mucosal CGRP-immunoreactive nerves were found in the epithelium of both proximal and distal esophagus, but were located more superficially in the proximal mucosa compared to the distal (11.5(SD7) vs. 21.7(SD5) cells layers from lumen, p=0.002). Conclusion Mucosal barrier integrity is similar in proximal and distal esophagus, but proximal mucosal afferent nerves are in a more superficial location. The enhanced sensitivity to reflux-evoked symptoms of the proximal esophagus most likely has an anatomical basis.
- Mucosal integrity
- Afferent nerves
- peripheral sensitization
- gastroesophageal reflux disease
- Copyright © 2014, American Journal of Physiology- Gastrointestinal and Liver Physiology