Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 30, Issue 3, Pages -Publisher
WILEY
DOI: 10.1111/nmo.13163
Keywords
autonomic nervous system; colitis; denervation; nerve stimulation
Funding
- Galvani Bioelectronics
- MSCA-ITN [641665]
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BackgroundVagus nerve stimulation is currently clinically evaluated as a treatment for inflammatory bowel disease. However, the mechanism by which this therapeutic intervention can have an immune-regulatory effect in colitis remains unclear. We determined the effect of intestine-specific vagotomy or intestine-specific sympathectomy of the superior mesenteric nerve (SMN) on dextran sodium sulfate (DSS)-induced colitis in mice. Furthermore, we tested the efficacy of therapeutic SMN stimulation to treat DSS-induced colitis in rats. MethodsVagal and SMN fibers were surgically dissected to achieve intestine-specific vagotomy and sympathectomy. Chronic SMN stimulation was achieved by implantation of a cuff electrode. Stimulation was done twice daily for 5minutes using a biphasic pulse (10Hz, 200A, 2ms). Disease activity index (DAI) was used as a clinical parameter for colitis severity. Colonic cytokine expression was measured by quantitative PCR and ELISA. Key ResultsIntestine-specific vagotomy had no effect on DSS-induced colitis in mice. However, SMN sympathectomy caused a significantly higher DAI compared to sham-operated mice. Conversely, SMN stimulation led to a significantly improved DAI compared to sham stimulation, although no other parameters of colitis were affected significantly. Conclusions & InferencesOur results indicate that sympathetic innervation regulates the intestinal immune system as SMN denervation augments, and SMN stimulation ameliorates DSS-induced colitis. Surprisingly, intestine-specific vagal nerve denervation had no effect in DSS-induced colitis.
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