1. The pathogenesis of heartburn in nonerosive reflux disease: A unifying hypothesis 
William J. Barlow, Roy C. Orlando 
Gastroenterology 
Volume 128, Issue 3, Pages (March 2005)
DOI: /j.gastro
Copyright © 2005 American Gastroenterological Association Terms and Conditions

2. Figure 1
(A and B) Transmission electron micrographs showing the differences in size of the intercellular spaces for normal (A) and nonerosive acid-damaged (B) esophageal epithelia (original magnification 9000×).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions

3. Figure 2
Unifying hypothesis: The presence of abnormal tissue resistance—demonstrated by defects within the intercellular junctional complex between cells of the surface layers of esophageal (stratified squamous) epithelium—is shown to enable the ready diffusion of refluxed gastric acid (H+) into the intercellular space. Within this space, it encounters and activates chemosensitive nociceptors whose signals are transmitted via the spinal cord to the brain for symptom (heartburn) perception. Activation of the same nociceptors are also capable of initiating a short reflex arc to esophageal (longitudinal) smooth muscle as means of precipitating a sustained esophageal contraction.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2005 American Gastroenterological Association Terms and Conditions