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Neuronal control of experimental colitis occurs via sympathetic intestinal innervation
Author(s) -
Willemze R. A.,
Welting O.,
Hamersveld H. P.,
Meijer S. L.,
Folgering J. H. A,
Darwinkel H.,
Witherington J.,
Sridhar A.,
Vervoordeldonk M. J.,
Seppen J.,
Jonge W. J.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13163
Subject(s) - medicine , vagotomy , colitis , sympathectomy , denervation , stimulation , inflammatory bowel disease , large intestine , vagus nerve , gastroenterology , endocrinology , disease
Background Vagus 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. Methods Vagal 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 5 minutes using a biphasic pulse (10 Hz, 200 μA, 2 ms). Disease activity index ( DAI ) was used as a clinical parameter for colitis severity. Colonic cytokine expression was measured by quantitative PCR and ELISA . Key Results Intestine‐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 & Inferences Our 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.