High Expression of Calcitonin Gene-Related Peptide and Substance P in Esophageal Mucosa of Patients with Non-Erosive Ref
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ORIGINAL ARTICLE
High Expression of Calcitonin Gene-Related Peptide and Substance P in Esophageal Mucosa of Patients with Non-Erosive Reflux Disease Xiaorong Xu • Zhaoshen Li • Duowu Zou • Min Yang • Zhanju Liu • Xingpeng Wang
Received: 6 November 2011 / Accepted: 25 June 2012 / Published online: 9 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract Background Visceral hypersensitivity is an important etiology of non-erosive reflux disease (NERD). Calcitonin gene-related peptide (CGRP) and substance P (SP) are involved in the sensitization of afferent neuronal pathways. Aim The objectives of this study were to evaluate visceral hypersensitivity in NERD patients, investigate the association between visceral hypersensitivity and mucosal expression of SP and CGRP, and assess their involvement in the pathogenesis of NERD. Methods Twenty-six NERD patients and 12 healthy volunteers were recruited. Intraesophageal balloon distention was performed, and initial perception threshold (IPT) and threshold of discomfort (ToD) were determined. Immunohistochemical staining was used to measure the optical density (OD) of CGRP and SP-reactive levels in esophageal mucosa, and the numbers of CGRP and SPreactive neural fibers. Results IPT and ToD were 9.6 ± 4.8 and 12.3 ± 3.2 ml, respectively, in NERD patients, significantly lower than for controls (13.2 ± 7.5 and 21.6 ± 5.7 ml, P \ 0.05 and P \ 0.01, respectively). Mean OD values for CGRP and SP staining were significantly higher in NERD than for controls (both P \ 0.05) and, in NERD, were negatively correlated with IPT and ToD (all P \ 0.01). Numbers of CGRP and SPreactive neural fibers in esophageal submucosa of NERD patients were significantly increased (both P \ 0.05). X. Xu (&) Z. Liu X. Wang Department of Gastroenterology, Tenth People’s Hospital of Tongji University, Yanchang Road, Shanghai 200072, China e-mail: [email protected] Z. Li D. Zou M. Yang Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Conclusions Expression of esophageal epithelial CGRP and SP is increased, and correlates negatively with perception thresholds in NERD. These findings may aid understanding of peripheral visceral hypersensitivity and the development of new therapeutic approaches for management of NERD. Keywords Gastroesophageal reflux Esophageal balloon distension Visceral hypersensitivity Calcitonin generelated peptide (CGRP) Substance P (SP)
Introduction For more than half of patients with gastroesophageal reflux disease (GERD) no endoscopic abnormality is observed; these patients are defined as having so-called non-erosive reflux disease (NERD). NERD patients complain of similar reflux symptoms, and more atypical symptoms and extraesophageal disorders (EED) than those with erosive reflux disease. Esophageal manometry and 24-h acid monitoring are normal in approximately 50 % of NERD patients. Moreover, they have poorer response to standard therapy with proton pump inhibitors (PPI) [1–3]. Similar to other
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