Control of colonic motility using electrical stimulation to modulate enteric neural activity

Bradley B. Barth, Lee Travis, Nick J. Spencer, Warren M. Grill

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1 Citation (Scopus)

Abstract

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and 1) determine the refractory periods of MCs, 2) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and 3) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs. 70.6 ± 15.7 s, P = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% confidence interval (CI) = 2.8–5.7 s, R2 = 0.7315, n = 8). Electrical stimulation applied during fluid distention-evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility. NEW & NOTEWORTHY Maintained physiological distension of the isolated mouse colon induces rhythmic cyclic myoelectric complexes (MCs). MCs evoked repeatedly by closed-loop electrical stimulation entrain MCs more frequently than spontaneously occurring MCs. Electrical stimulation delivered at the onset of a contraction temporarily suppresses the propagation of MC contractions. Controlled electrical stimulation can either evoke MCs or temporarily delay MCs in the isolated mouse colon, depending on timing relative to ongoing activity.

Original languageEnglish
Pages (from-to)G675-G687
Number of pages13
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume320
Issue number4
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Funding Information:
This work was financially supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01DK119795 (to W.M.G.), National Health and Medical Research Council Grant 1156416 (to N.J.S.), Australian Research Council Grant DP190103628 (to N.J.S.), and the Department of Biomedical Engineering at Duke University.

Publisher Copyright:
Copyright © 2021 the American Physiological Society

Keywords

  • Closed-loop controller
  • Colonic motor complex
  • Enteric nervous system
  • Neurogastroenterology
  • Neuromodulation

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