title: High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease.
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.
  
  
  OBJECTIVE
  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 SP-reactive 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 SP-reactive neural fibers in esophageal submucosa of NERD patients were significantly increased (both P < 0.05).
  
  
  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.
authors.affiliation: Department of Gastroenterology, Tenth People's Hospital of Tongji University, Yanchang Road, Shanghai, 200072, China. xrxu2011@sina.com
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Xu
authors.forename: Zhaoshen
authors.initials: Z
authors.lastname: Li
authors.forename: Duowu
authors.initials: D
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D012684:Sensory Thresholds / Q000502:physiology; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide