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, 8 (1), e14294

Sacral Nerve Stimulation Prompts Vagally-Mediated Amelioration of Rodent Colitis

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Sacral Nerve Stimulation Prompts Vagally-Mediated Amelioration of Rodent Colitis

Trisha S Pasricha et al. Physiol Rep.

Abstract

Neuromodulation based on the vagal anti-inflammatory reflex has emerged as an exciting therapeutic approach for chronic inflammatory diseases. However, it is unclear whether direct stimulation of the vagus or of pelvic nerves coming from sacral roots, providing the bulk of colonic parasympathetic innervation, is the best approach. We hypothesized that sacral nerve stimulation (SNS) would be an effective treatment for colitis. Age and sex-matched Sprague-Dawley rats were administered 5% dextran sulphate sodium (DSS) in drinking water ad libitum for 7 days. A group of rats was sacrificed after DSS treatment, and the remaining rats were randomized to either sham-SNS or SNS groups, which were performed for 1 hr daily for 10 days. Stimulations were delivered via chronically implanted electrodes using an 8-channel universal pulse generator. Sacral nerve stimulation promoted recovery of colitis demonstrated by decreased disease activity index, myeloperoxidase activity, tissue TNF-alpha, and histological scores as well as an increased colonic M2 macrophage population. Heart rate variability analysis demonstrated a decrease in low frequency and increase in high frequency with SNS, corresponding to increased vagal tone. Additionally, plasma pancreatic peptide was increased and norepinephrine was decreased after SNS in colitis while colon tissue acetylcholine was increased with SNS. This is the first study to the best of our knowledge that demonstrates the benefit of SNS with autonomic mediation. SNS alters the expression of inflammatory cytokines and macrophages as well as modulates neurotransmitters involved in systemic inflammation.

Keywords: DSS colitis; heart rate variability; inflammatory bowel disease; sacral nerve stimulation; sympathovagal balance.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Study timeline. Rats were treated for 7 days with 5% DSS during which daily DAI scores and HRV were measured. After this, rats were either treated with sacral nerve stimulation or sham‐sacral nerve stimulation for an additional 10 days. Measurements of DAI and HRV continued during this time period. At the end of the study on day 17, rats were sacrificed and tissue and serum were collected for analysis
Figure 2
Figure 2
Sacral nerve stimulation promotes recovery of colitis. (a) DAI is significantly improved with SNS within 5 days of treatment. (b) Overall histological scores are significantly improved and colon lengths trend toward improvement with SNS. (c) Tissue TNF‐alpha and MPO activity, a marker of inflammation, are significantly decreased with SNS. (d) Macrophage population and representative colon biopsies demonstrating increased M2 macrophages after SNS (H&E with CD68 and CD206 staining, 100×). Mean values with standard deviation are shown. * denotes p < .05
Figure 3
Figure 3
Sacral nerve stimulation is associated with increased parasympathetic activity. (a) LF/HF ratio is significantly reduced after SNS in colitis with a decrease in LF and increase in HF. (b) Plasma PP is increased and NE is decreased after SNS in colitis. (c) Colon tissue Ach is significantly increased with SNS. (d) Plasma VIP, iNOS, and substance p are significantly regulated by SNS. Mean values with standard deviation are shown. * denotes p < .05

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