Effects of 1-week sacral nerve stimulation on the rectal intestinal epithelial barrier and neuromuscular transmission in a porcine model

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Abstract

Background

Sacral nerve stimulation (SNS) is a validated treatment for fecal incontinence, although the mechanism of action remains unknown. Short-term effects of SNS on the intestinal epithelial barrier (IEB) have been reported previously. The aim of our study was to assess the impact of a 1-week SNS on the IEB in a preclinical model.

Methods

Fourteen pigs were implanted for bilateral SNS. Seven pigs received 7-day stimulation, whereas the remaining animals received no stimulation. Rectal biopsies were performed before and after SNS. We assessed IEB permeability, mucosal tight junction and cytokine mRNA expression, IL-6 production in an organotypic culture model, and neuromuscular transmission in muscle strips.

Key Results

IEB permeability was not modified after stimulation, as compared with baseline. The PAR-induced increase in IEB permeability and the mucosal ZO-1 mRNA decrease observed in the controls were not observed into the stimulated group. Cytokine overexpression was not observed in the mucosa in either group. SNS decreased IL-6 production in the organotypic culture model. In the stimulated group, the area-under-the-curve of the EFS-induced contractile response was significantly increased.

Conclusions & Inferences

The main conclusions of our work are (i) the successful development of a preclinical model of bilateral SNS and (ii) in physiological conditions, 1-week SNS did not lead to functional changes in the mucosa. While under stress-induced conditions, SNS modified the properties of the IEB, leading to a decrease in its permeability. Neuromuscular transmission was modified by SNS, leading to neuronal hyperexcitability. These results add evidence to the reinforcement of the IEB by SNS.

Conclusions & Inferences

Our work has successfully developed a preclinical model of bilateral SNS for which, in physiological conditions, 1-week SNS did not lead to functional changes in the mucosa. While under stress-induced conditions, SNS modified the properties of the IEB, leading to a decrease in its permeability. Our results add evidence to the reinforcement of the IEB by SNS.

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