Abstract

BackgroundThe colon has distinct proximal (pC), transverse (tC), distal (dC) and colorectal regions. The different colonic regions response to neuromodulation is not well known. Interest in neuromodulation, as an alternative therapy to refractory gut motility disorders is increasing, although efficacy and optimal stimulation parameters remain elusive.AimDetermine the effect of neuromodulation (direct colon tissue or autonomic nerves) on the colonic regional phasic contractions in a porcine model.MethodsAnesthetized male Yucatan pigs (6 months old, 25–30 kg) were used. Following laparotomy, still manometry catheters (Millar) were placed in the pC, tC, dC and the anal canal (AC). The colonic luminal phasic pressure changes were monitored under basal conditions, during and after electrical stimulation (ES). Direct colon tissue ES was done using planar flexible multi‐electrode array panels (10Hz, 2ms, 15mA). In separate groups, the celiac branch of the vagus nerve (CBVN, 2 Hz, 5mA, 0.3–4ms, pulse train) or sacral nerve roots (S2, 30Hz, 0.3ms, 0.5mA) was electrically stimulated with or without concurrent afferent anodal nerve block (200Hz, 0.1ms, 2mA, for CBVN). Phasic pressure changes were analyzed using area under the curve of contraction (AUC) and fast Fourier transform (FFT) to obtain the frequency spectra. Contraction frequency power changes were analyzed using repeated measures 2‐way ANOVA and Sidak’s post hoc test.ResultsIn anesthetized male pigs, the basal activity of the colon is characterized by prominent phasic pressure frequencies (1–12cpm) with dominant frequency power of the 1–6cpm in all the 3 regions monitored (pC, tC, dC). Direct colon tissue ES at all regions increased area AUC however only pC and tC increased the respective region’s dominant frequency band power (1–6cpm) (pC: 1cpm p<0.05, 2 cpm p< 0.001, 3 cpm p<0.01 vs baseline; tC: 2 cpm, p<0.05 vs baseline). CBVN ES triggered pancolonic increase in AUC and caused a significant increase in the 1–3cpm power at the tC (2 cpm p<0.01, 3 cpm p<0.01 vs baseline). S2 stimulation selectively increased AUC at dC and the anal canal (Fig. 1). Afferent block reduced the CBVN‐induced increased AUC in the pC and tC and the power at tC.ConclusionBoth direct colon tissue and celiac branch of the vagus nerve ES increase AUC and power of the dominant frequency band (1–6cpm). S2 stimulation selectively increased AUC of the dC and the anal canal. The physiological significance of the region specific increase in the colonic AUC and power of dominant contraction frequency band in response to neuromodulation warrants further studies in non‐anesthetized state.Support or Funding InformationNIH SPARC grant #OT2OD24899Heat map of colonic luminal pressure area under the curve of contraction in response to sacral S2 nerve stimulation in anesthetized adult male Yucatan pigs. Heat map (percentage of baseline) is generated from 3 pigs at baseline (30 min), during stimulation (10 min) and post stimulation (30 min) periods.Figure 1

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