Quantitative Assessment and Characterization of Visceral Hyperalgesia Evoked by Esophageal Balloon Distention and Acid Perfusion in Patients With Functional Heartburn, Nonerosive Reflux Disease, and Erosive Esophagitis

Background and Objectives: The role of esophageal hypersensitivity in functional heartburn (FH) with negative pH test, negative symptom index, and the proton pump inhibitor (PPI) failure has not been established. The aim of this study was to investigate the characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with FH, nonerosive reflux disease, and erosive esophagitis and further characterize the pathophysiologic mechanism of FH. Methods: A total of 21 FH patients (with esophageal acid exposure <3.1% and a symptom index < 50% and nonresponse to a therapeutic trial with proton pump inhibitors, 25 Nonerosive reflux disease (NERD) patients (with esophageal acid exposure >4%), 23 erosive esophagitis (EE) patients (LA grade B to D), and 18 healthy controls were recruited in the study. Mechanosensitivity including the initial perception threshold (IPT) and pain threshold (PT) was evaluated by using a Barostat with a double-random staircase distension protocol. Chemosensitivity was graded along a visual analog scale after perfusion of saline and 0.1 N HCl. Results: The baseline IPTs and PTs were all lower in patients with FH, NERD, and EE than in the controls (all P<0.01). In addition, the baseline PT in FH patients was significantly lower than those in NERD (P=0.015) and EE patients (P<0.001). After acid perfusion, the mean symptom intensity scores were significantly greater in patients with FH, NERD, and EE than those in the controls (all P<0.001). The postacid perfusion IPTs in patients with FH, NERD, and EE were all significantly lower than the corresponding baseline values (all P<0.01). The PTs in FH (P=0.026) and EE patients (P<0.001) were significantly lower than the corresponding baseline values. Moreover, the postacid perfusion PT was significantly lower in FH patients than in NERD patients (P<0.001). Conclusions: FH patients are more sensitive to mechanical or chemical stimuli than NERD patients. Sensitization of esophageal acid-sensitive chemoreceptors may exert a significant influence on the pressure-sensitive mechanoreceptors, and there is the cooperative interaction in the process of esophageal visceral hyperalgesia.