Vagus nerve stimulation attenuates caerulein-induced acute pancreatitis in mice via a CGRP-dependent mechanism
FENG Jiaming
ZHANG Chao
XU Shenhui
LI Jing
LOU Lijun
LUO Hui
PAN Yanglin
Abstract：Objective To investigate the protective effect of vagus nerve stimulation(VNS)on caerulein-induced acute pancreatitis(AP)in mice.Methods Male C57BL/6 mice were randomly divided into four groups:control group,caerulein group,caerulein+VNS group,and caerulein+VNS+methyllycaconitine citrate(MLA)group,with 6 mice in each group.The AP model was established by intraperitoneal injections of caerulein(50 μg/kg).VNS was administered for 30 min following the first and seventh injections of caerulein.Histomorphological changes in pancreatic tissue were observed by HE staining and quantified using a histopathological scoring system.Serum levels of lipase and amylase were measured using an automated biochemical analyzer.Infiltration of inflammatory cells was assessed by immunohistochemical staining and counting of myeloperoxidase(MPO)-positive and F4/80-positive cells.Serum levels of inflammatory cytokines and changes of vagus nerve(VN)neurotransmitters were detected by ELISA.The effect of calcitonin gene-related peptide(CGRP)on the protective role against AP in mice was investigated using intraperitoneal injection of 1 mg/kg CGRP.Results VNS effectively activated the dorsal motor nucleus of the VN and the nucleus tractus solitarius in mice.In the caerulein-induced AP model,VNS intervention significantly reduced pancreatic histopathological scores,accompanied by decreased levels of serum amylase,lipase,MPO-positive cell count,F4/80-positive cell count,and inflammatory cytokines(P<0.05).Co-treatment with MLA during VNS failed to significantly weaken the protective effect of VNS on AP.Compared with the control and caerulein groups,acetylcholine and CGRP levels were significantly elevated in the caerulein+VNS group and caerulein+VNS+MLA group(P<0.05).Further intervention experiments showed that intraperitoneal administration of CGRP markedly alleviated pancreatic tissue injury(P<0.05).Conclusion VNS alleviates local and systemic inflammation in caerulein-induced AP in mice.It is the first to reveal that this protective effect may be associated with the release of cholinergic neurotransmitters and neuropeptides such as CGRP upon VN activation.Exogenous CGRP supplementation attenuates pancreatic tissue injury in AP,suggesting its potential therapeutic value.
Keywords：acute pancreatitisvagus nerve stimulationcaeruleinneurotransmittercholinergic anti-inflammatory pathwayacetylcholinecalcitonin gene-related peptidevasoactive intestinal peptide
Publication Date：2026-01-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 93-100 )