Vagus Nerve Stimulation Reduces Indomethacin-Induced Small Bowel Inflammation

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Caravaca, April S.Karolinska Institutet (author)

Vagus Nerve Stimulation Reduces Indomethacin-Induced Small Bowel Inflammation

Article/chapterEnglish2022

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2022-01-12
Frontiers Media SA,2022
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:liu-182763
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-182763URI
https://doi.org/10.3389/fnins.2021.730407DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:148636507URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agencies|SetPoint Medical, Inc.; Bengt Ihre Research Fellowship; Stockholm County Council ALFStockholm County Council [20180565]; MedTechLabs, Stockholm
Crohns disease is a chronic, idiopathic condition characterized by intestinal inflammation and debilitating gastrointestinal symptomatology. Previous studies of inflammatory bowel disease (IBD), primarily in colitis, have shown reduced inflammation after electrical or pharmacological activation of the vagus nerve, but the scope and kinetics of this effect are incompletely understood. To investigate this, we studied the effect of electrical vagus nerve stimulation (VNS) in a rat model of indomethacin-induced small intestinal inflammation. 1 min of VNS significantly reduced small bowel total inflammatory lesion area [(mean +/- SEM) sham: 124 +/- 14 mm(2), VNS: 62 +/- 14 mm(2), p = 0.002], intestinal peroxidation and chlorination rates, and intestinal and systemic pro-inflammatory cytokine levels as compared with sham-treated animals after 24 h following indomethacin administration. It was not known whether this observed reduction of inflammation after VNS in intestinal inflammation was mediated by direct innervation of the gut or if the signals are relayed through the spleen. To investigate this, we studied the VNS effect on the small bowel lesions of splenectomized rats and splenic nerve stimulation (SNS) in intact rats. We observed that VNS reduced small bowel inflammation also in splenectomized rats but SNS alone failed to significantly reduce small bowel lesion area. Interestingly, VNS significantly reduced small bowel lesion area for 48 h when indomethacin administration was delayed. Thus, 1 min of electrical activation of the vagus nerve reduced indomethacin-induced intestinal lesion area by a spleen-independent mechanism. The surprisingly long-lasting and spleen-independent effect of VNS on the intestinal response to indomethacin challenge has important implications on our understanding of neural control of intestinal inflammation and its potential translation to improved therapies for IBD.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Crohns disease; inflammatory reflex; vagus nerve stimulation; small bowel; indomethacin; cholinergic anti-inflammatory pathway; bioelectronic medicine; inflammatory bowel disease

Added entries (persons, corporate bodies, meetings, titles ...)

Levine, Yaakov A.Karolinska Institutet (author)
Drake, AnnaSetPoint Med Inc, CA 91355 USA (author)
Eberhardson, MichaelKarolinska Institutet,Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken,Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden(Swepub:liu)miceb31 (author)
Olofsson, Peder S.Karolinska Institutet (author)
Karolinska InstitutetSetPoint Med Inc, CA 91355 USA (creator_code:org_t)

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