Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 31, Issue 10, Pages -Publisher
WILEY
DOI: 10.1111/nmo.13676
Keywords
autonomic function; inflammatory bowel disease; sacral nerve stimulation
Funding
- Defense Advanced Research Projects Agency (DARPA) BTO under the [Space and Naval Warfare Systems Center, Pacific OR DARPA Contracts Management Office] [N66001-15-2-4059]
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Background Vagal nerve stimulation (VNS) was reported to have a therapeutic potential for inflammatory bowel disease (IBD). This study was designed to determine effects and mechanisms of SNS on colonic inflammation of in rodent models of IBD and compare the difference among SNS, VNS, and SNS plus VNS. Methods Intestinal inflammation in rats was induced by intrarectal administration of TNBS (2,4,6-Trinitrobenzenesulfonic acid) on the first day. Five days after intrarectal TNBS, the rats were treated with sham-VNS, VNS, Sham-SNS, SNS, and SNS + VNS for 10 days. In another experiment, after 10 days of 4% DSS (dextran sodium sulfate) in drinking water, rats were treated with 10-day sham-SNS and SNS. Various inflammatory responses were assessed; mechanisms involving autonomic functions and inflammatory cytokines were investigated. Key Results (a) VNS, SNS, and VNS + SNS significantly and equally decreased the disease activity index and macroscopic scores, and normalized colon length; (b) IL-10 was decreased by TNBS but increased with SNS, VNS, and SNS + VNS; pro-inflammatory cytokines, IL-6, IL-17A, MCP-1 and TNF-alpha, were increased by TNBS but decreased with SNS, VNS, and SNS + VNS (P < .05); MPO activity was decreased by SNS, VNS, and SNS + VNS; (c) SNS, VNS, and SNS + VNS remarkably increased vagal activity that was suppressed by TNBS (P < .05); (d) smilar SNS effects were noted in rats with DSS-induced colitis. Conclusions & Inferences SNS presents similar anti-inflammatory effects as VNS by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the autonomic pathway. Similar to VNS, SNS may also have a therapeutic potential for colonic inflammation.
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