Electrical stimulation of gut motility guided by an in silico model.

Published

Journal Article

OBJECTIVE:Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases-ranging from Parkinson's Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood. Here we develop an integrated neuromechanical model of the ENS and assess neurostimulation strategies for enhancing gut motility, validated by in vivo experiments. APPROACH:The computational model included a network of enteric neurons, smooth muscle fibers, and interstitial cells of Cajal, which regulated propulsion of a virtual pellet in a model of gut motility. MAIN RESULTS:Simulated extracellular stimulation of ENS-mediated motility revealed that sinusoidal current at 0.5 Hz was more effective at increasing intrinsic peristalsis and reducing colon transit time than conventional higher frequency rectangular current pulses, as commonly used for neuromodulation therapy. Further analysis of the model revealed that the 0.5 Hz sinusoidal currents were more effective at modulating the pacemaker frequency of interstitial cells of Cajal. To test the predictions of the model, we conducted in vivo electrical stimulation of the distal colon while measuring bead propulsion in awake rats. Experimental results confirmed that 0.5 Hz sinusoidal currents were more effective than higher frequency pulses at enhancing gut motility. SIGNIFICANCE:This work demonstrates an in silico GI neuromuscular model to enable GI neuromodulation parameter optimization and suggests that low frequency sinusoidal currents may improve the efficacy of GI pacing.

Full Text

Duke Authors

Cited Authors

  • Barth, BB; Henriquez, CS; Grill, WM; Shen, X

Published Date

  • December 2017

Published In

Volume / Issue

  • 14 / 6

Start / End Page

  • 066010 -

PubMed ID

  • 28816177

Pubmed Central ID

  • 28816177

Electronic International Standard Serial Number (EISSN)

  • 1741-2552

International Standard Serial Number (ISSN)

  • 1741-2560

Digital Object Identifier (DOI)

  • 10.1088/1741-2552/aa86c8

Language

  • eng