The effect of colonic tissue electrical stimulation and celiac branch of the abdominal vagus nerve neuromodulation on colonic motility in anesthetized pigs

Abstract

Background: Knowledge on optimal electrical stimulation (ES) modalities and regionspecific functional effects of colonic neuromodulation is lacking. We aimed to map the regional colonic motility in response to ES of (a) the colonic tissue and (b) celiac branch of the abdominal vagus nerve (CBVN) in an anesthetized porcine model. Methods: In male Yucatan pigs, direct ES (10 Hz, 2 ms, 15 mA) of proximal (pC), transverse (tC), or distal (dC) colon was done using planar flexible multi-electrode array panels and CBVN ES (2 Hz, 0.3-4 ms, 5 mA) using pulse train (PT), continuous (10 min), or square-wave (SW) modalities, with or without afferent nerve block (200 Hz, 0.1 ms, 2 mA). The regional luminal manometric changes were quantified as area under the curve of contractions (AUC) and luminal pressure maps generated. Contractions frequency power spectral analysis was performed. Contraction propagation was assessed using video animation of motility changes. Key Results: Direct colon ES caused visible local circular (pC, tC) or longitudinal (dC) muscle contractions and increased luminal pressure AUC in pC, tC, and dC (143.0 ± 40.7%, 135.8 ± 59.7%, and 142.0 ± 62%, respectively). The colon displayed prominent phasic pressure frequencies ranging from 1 to 12 cpm. Direct pC and tC ES increased the dominant contraction frequency band (1-6 cpm) power locally. Pulse train CBVN ES (2 Hz, 4 ms, 5 mA) triggered pancolonic contractions, reduced by

Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system

“…The copyright holder for this preprint this version posted February 25, 2022. ; https://doi.org/10.1101/2022.02.24.480770 doi: bioRxiv preprint implicated in the VNS-altered colonic physiological functions as we reported before 17 , suggesting that human colonic functions and neuromodulation could be modeled in the porcine.…”

“…The cross-comparison of the regional transcriptomic profiling between porcine and human indicates that the myenteric ganglia in proximal or distal colon express a conserved core gene program of orthologous genes from porcine to human with regional heterogeneity. Interestingly, VNS on the porcine modulates the conserved transcriptional program in the myenteric ganglia of proximal or distal colon, which may be implicated in the VNS-altered colonic physiological functions as we reported before 17 , suggesting that human colonic functions and neuromodulation could be modeled in the porcine.…”

“…In addition, colonic functions are modulated through parasympathetic innervation, responsible for regulating colonic secretion and motility 16 . We have recently reported that electrical vagal nerve stimulation (VNS) triggered pan-colonic contractions in the porcine 17 . However, it is unknown how such VNS influences colonic transcriptional programs and whether the impacts of VNS are region-specific.…”

Bio-impedance method to monitor colon motility response to direct distal colon stimulation in anesthetized pigs

“…Furthermore, the dominant frequencies (with most power/magnitude) of bio-impedance were identified and found to be shifted after the stimulation. The experimental results furthermore indicated the correlations between the proposed bio-impedance and the manometry approaches while dealing with the data reported in 23 , which demonstrates its potential application in colonic motility monitoring.…”

“…Electrical stimulation is a viable therapy for colonic motor disorders, particularly for patients who are refractory to traditional pharmaceutical treatments. As interest grows, a number of studies on colonic electrical stimulation have been conducted, which showed promising outcomes under different conditions 13 – 23 . In most of the current studies, the effectiveness of the technique was assessed mainly via colonic motility evaluation.…”