Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease.

GOALS: To investigate the features of nonerosive reflux disease (NERD). BACKGROUND: NERD is not considered as a milder form of erosive gastro-esophageal reflux disease (eGERD). Although the prevalence of NERD was reported to be high in our country, there have been very few studies about NERD. STUDY: We performed upper gastrointestinal endoscopy to confirm the diagnosis of GERD. The modified acid perfusion test and saline perfusion test were performed in 7 control subjects, 14 NERD, and 11 eGERD patients. The stimulus-response function to acid and saline was quantified by the duration of typical symptom perception (minutes), total sensory intensity rating (0 to 10), and the perfusion sensory score (SS), which was defined as the product of minutes and the sensory intensity rating. RESULTS: The mean value of SS by saline was 0 in control subjects, 12.0 in NERD patients, and 1.5 in eGERD patients (P<0.01 control vs. NERD, P<0.01 NERD vs. eGERD). The mean SS with acid was 0.9 in control subjects, 52.5 in NERD patients, and 23.0 in eGERD patients (P<0.01 control vs. NERD, control vs. eGERD, P<0.05 NERD vs. eGERD). A statistically significant association was shown between the acid and saline perfusion SSs with a correlation coefficient value of r=0.57 in the NERD group (P<0.05). CONCLUSIONS: Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BACKGROUND: The esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis. METHODS: Chronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats. RESULTS: In the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers. CONCLUSIONS: The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.