Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis

Lei Tu, Payam Gharibani, Jieyun Yin, Jiande D.Z. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. Methods: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. Key Results: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. Conclusions & Inferences: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.

Original languageEnglish (US)
Article numbere13916
JournalNeurogastroenterology and Motility
Volume32
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • colonic permeability
  • cytokines
  • enteric neurons
  • inflammatory bowel diseases
  • mast cells
  • sacral nerve stimulation
  • ulcerative colitis

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Fingerprint Dive into the research topics of 'Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis'. Together they form a unique fingerprint.

Cite this