OBJECTIVE: More than half the patients with gastroesophageal reflux disease (GERD) show no endoscopic abnormality now termed non-erosive reflux disease (NERD). The aim of this study was measure the expression level of substance P (SP) and to evaluate the role of SP in the pathogenesis of visceral hypersensitivity in NERD.
METHODS: Subjects with symptoms such as heartburn and acid regurgitations of 3 months duration underwent endoscopic and those with endoscopically visible signs of esophagitis (Los Angeles A¨CD) or Barrett¡¯s esophagus were excluded. Immune-histological stain assay was used to measure the optical density (OD) of SP-reactive level in esophageal specimens from endoscopic normality patients (N 26), and SP-reactive neural fibers were calculated, too. Esophageal manometry, Bernstein testing, intraesophageal balloon distention (IEBD), and 24-h esophageal pH monitoring were underwent in these patients. 10 controls were enrolled in this study. RESULTS: Esophageal 24h pH monitoring result was normal in 52% of these NERD subjects. Heartburn developed in 85% of patients during Bernstein acid infusion, Initial perception threshold and maximally tolerated pain threshold of NERD patients was 9.6¡À4.8 ml and 12.3¡À3.2ml,significantly decreased than those of control, 13.2¡À7.5 ml and 21.6¡À5.7 ml, respectively.(P<0.007, P<0.003) . The mean OD value of SP-positive contents in NERD (0.42¡À0.12)was significantly increased than control subjects(0.29¡À0.05) ,respectively (P< 0.02) ,the number ofSP-positive neural fibers (4.89¡À2.76) observed in NERD patients¡¯ esophageal submucosa was significantly increased than that of thecontrol(3.01¡À1.96), (P< 0.05). The mean OD value of NERD was negatively related with the initial perception threshold and maximally tolerated pain threshold,r values were - 0.700£¨P<0.01£©. CONCLUSIONS: A significant lower threshold for esophageal sensation and pain were observed in NERD patients , the pathogenesis of NERD symptoms may associated with visceral hypersensitivity to mechanical or chemical stimuli. SP may be responsible at least in the primary afferents level.