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Role of TRPV 1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease
Author(s) -
Silva R. O.,
Bingana R. D.,
Sales T. M. A. L.,
Moreira R. L. R.,
Costa D. V. S.,
Sales K. M. O.,
Brito G. A. C.,
Santos A. A.,
Souza M. Â. N.,
Soares P. M. G.,
Sifrim D.,
Souza M. H. L. P.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13340
Subject(s) - nerd , trpv1 , medicine , inflammation , intestinal permeability , pathology , gastroenterology , gerd , reflux , transient receptor potential channel , receptor , disease
Background Microscopic inflammation and impairment of the esophageal epithelial barrier are considered relevant for perception of symptoms in patients with nonerosive reflux disease ( NERD ). In these patients, the receptor transient receptor potential vanilloid 1 ( TRPV 1) is overexpressed in the esophageal mucosa, but its role is not yet fully understood. We evaluated the role of TRPV 1 in esophageal inflammation and mucosal barrier impairment in a murine model of NERD . Methods Nonerosive reflux disease was surgically induced in Swiss mice by pyloric substenosis and ligature of the gastric fundus, and the mice were killed 7 days post surgery. The experimental groups were: I, sham surgery (negative control); II, NERD untreated; III and IV, NERD + SB 366791 or capsazepine ( TRPV 1 antagonists); and V, NERD + resiniferatoxin (for long‐term desensitization of TRPV 1). The esophagus was collected for western blotting and histopathology and for evaluation of wet weight, myeloperoxidase ( MPO ), keratinocyte‐derived chemokine ( KC ), transepithelial electrical resistance ( TEER ), and basal permeability to fluorescein. Key Results Compared to sham, NERD mice had increased esophageal wet weight and MPO and KC levels. The mucosa had no ulcers but exhibited inflammation. NERD mice showed mucosal TRPV 1 overexpression, a more pronounced decrease in TEER at pH 0.5 (containing pepsin and taurodeoxycholic acid), and increased basal permeability. Pharmacological modulation of TRPV 1 prevented esophageal inflammation development, TEER changes by acidic exposure, and increase in esophageal permeability. Conclusions & Inferences The TRPV 1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV 1 might be a pharmacological target in patients with NERD .