Systematic review of small intestine pacing parameters for modulation of gut function

Abstract

Background and Purpose:The efficacy of conventional treatments for severe and chronic functional motility disorders remains limited. High-energy pacing is a promising alternative therapy for patients that fail conventional treatment. Pacing primarily regulates gut motility by modulating rhythmic bio-electrical events called slow waves.While the efficacy of this technique has been widely investigated on the stomach, its application in the small intestine is less developed. This systematic review was undertaken to summarize the status of small intestinal pacing and evaluate its efficacy in modulating bowel function through preclinical research studies. Methods:The literature was searched using Scopus, PubMed, Ovid, Cochrane, CINAHL, and Google Scholar. Studies investigating electrophysiological, motility, and/or nutrient absorption responses to pacing were included. A critical review of all included studies was conducted comparing study outcomes against experimental protocols. Results:The inclusion criteria were met by 34 publications. A range of pacing parameters including amplitude, pulse width, pacing direction, and its application to broad regional small intestinal segments were identified and assessed. Out of the 34 studies surveyed, 20/23 studies successfully achieved slow-wave entrainment, 9/11 studies enhanced nutrient absorption and 21/27 studies modulated motility with pacing. Conclusion:Small intestine pacing shows therapeutic potential in treating disorders such as short bowel syndrome and obesity. This systematic review proposes standardized protocols to maximize research outcomes and thereby translate to human studies for clinical validation. The use of novel techniques such as high-resolution electrical, manometric, and optical mapping in future studies will enable a mechanistic understanding of pacing.

High-Energy Pacing in the Jejunum Elicits Pulsatile Segmental Contractions

“…Significant research has been conducted on the small intestine to determine the effect of pacing on the GI TBME-00364-2023 motility [13]. However, investigators primarily mapped the rate of emptying [14], [35], [36], or used low-resolution manometry to determine the motility response [15], [19], [37].…”

“…On the other hand, high-energy pacing targets the interstitial cells of Cajalthe pacemaker cells of the GI tractand therefore, can induce contractions if sufficient energy levels are applied [9], [10]. High-energy pacing has been shown to modulate GI function including: motility, absorbency, and bio-electrical activity [11]- [13]. The ability to modulate the contractile response of the small intestine via pacing is of importance to develop novel therapies for disorders such as post-operative ileus and chronic intestinal pseudo-obstruction.…”

Optimization of pacing parameters to entrain slow wave activity in the pig jejunum

“…Small intestine pacing has also been investigated for its clinical potential and has reported success in modulating the electrical and motility responses alongside absorption rates 18 – 20 . Electrical activity has been modulated to normalize dysrhythmias in intact and transected intestinal segments 20 – 22 .…”

“…These findings are highly relevant in treating multi-factorial conditions such as prolonged post-operative ileus and short bowel syndrome, which can be challenging to treat with conventional approaches 26 , 27 . A recent systematic review revealed pacing orientation plays a key role in enhancing and inhibiting these responses, which highlights the critical role of individual pacing parameters and the need for their systematic evaluation 18 .…”

“…However, pacing response of the small intestine is yet to be investigated using high-resolution techniques to determine optimal settings. The need for appropriate high-resolution electrode arrays and implantable devices has been previously highlighted 18 , and a novel framework which enables high-resolution electrical mapping was recently introduced 33 .…”