Colonic mucosal N-methyl-D-aspartic receptor participates in pathogenesis of irritable bowel syndrome

Background: Abdominal pain caused by visceral hypersensitivity is an important characteristic of patients with irritable bowel syndrome (IBS). N-methyl-D-aspartic receptor (NMDAR) plays an important role in visceral hypersensitivity both in central and peripheral nerve systems, but the use of NMDAR antagonist is limited by its adverse reaction in central nervous system.
Methods: Rectosigmoid biopsies were collected from patients with IBS and healthy controls (approved by the ethics committee). Abdominal pain was quantified by a validated questionnaire. The presence and quantitative analysis of NMDAR in the mucosa were assessed by immunohistochemistry and western blot. Correlation between the expression of NMDAR and abdominal pain was assessed by Spearman rank correlation.
Results: Immunohistochemistry and western blot confirmed the high expression of NMDAR in colonic mucosa. Increased protein level of NMDAR was detected in IBS patients, as compared with controls (p<0.05). A significant correlation was observed between mucosal NMDAR expression level and the scores of abdominal pain (p<0.05).
Conclusions: Increased NDMAR in colonic mucosa is confirmed in IBS, which is significantly related to the abdominal pain. The upregulated expression of NMDAR may contribute to the pathogenesis of visceral hypersensitivity in IBS. Our primary study provides a novel therapeutic target for IBS.