Multi-targeting regulation of auricular vagus nerve stimulation on gastric hypersensitivity and gastric dysmotility in a rodent model of functional dyspepsia
Multi-targeting regulation of auricular vagus nerve stimulation
DOI:
https://doi.org/10.54844/gmiw.2022.0088Keywords:
Auricular vagus nerve stimulation; Functional dyspepsia; Visceral hypersensitivity; Gastric motility; Brain-gut peptide; Inflammatory cytokinesAbstract
Background: Evidences have shown the auricular vagus nerve stimulation (aVNS) is effective for functional dyspepsia (FD) recently. This study aimed to observe the mechanism of aVNS on facilitatory mediators of the inflammation in a rat model of functional dyspepsia. Methods: Thirty-six 5 d-old male Sprague Dawley rats were randomly divided into control groups (n = 12), model group (n = 12), aVNS group (n = 6) and sham-aVNS group (n = 6). Except for the control rats, all other rats were treated with iodoacetamide gavage. After the model was developed successfully, rats in aVNS group and sham-aVNS group received aVNS and sham-aVNS respectively, 30 min/1 time per day for 14 consecutive days. The control group and model group received no intervention. Gastric sensitivity after 1-week of intervention and gastric emptying after 2-week of intervention were adopted to assess the effect of aVNS. Brain-gut peptides, facilitatory mediators of the inflammation in serum were tested by ELISA, and α7 nicotinic acetylcholine receptor (α7-nAchR) in antrum tissue were tested by Immunohistochemistry to explore the mechanism of aVNS. Results: Compared with the control group, the gastric sensitivity was increased, gastric emptying decreased, and there was no structural damage in the gastric antrum in the model group. aVNS reduced visceral hypersensitivity and improved gastric emptying but not sham-aVNS. cholecystokinin, glucagon-like peptide-1, peptide, tumor necrosis factorα and interleukin 6 were all increased, while ghrelin and α7-nAchR decreased in model rats (P < 0.01 for all, compared with the control group). aVNS can normalize them. Conclusion: The aVNS can decrease the gastric sensitivity and increase gastric emptying, the mechanism was related to its regulation of brain-gut peptides and facilitatory mediators of the inflammation. The ameliorating effect was related to cholinergic mechanism.
References
Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal Disorders. Gastroenterology.2016;150(6):1380-1392.[PMID: 27147122 DOI: 10.1053/j.gastro.2016.02.011]
Ford AC, Marwaha A, Sood R, et al. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut.2015;64(7):1049-1057.[PMID: 25147201 DOI: 10.1136/gutjnl-2014-307843]
Ford AC, Marwaha A, Lim A, et al. What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis. Clin Gastroenterol Hepatol.2010;8(10):830-837.[PMID: 20541625 DOI: 10.1016/j.cgh.2010.05.031]
Ford AC, Mahadeva S, Carbone MF, et al. Functional dyspepsia. Lancet (London, England).2020;396(10263):1689-1702.[PMID: 33049222 DOI: 10.1016/S0140-6736(20)30469-4]
Moayyedi P, Lacy BE, Andrews CN, et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol.2017;112(7):988-1013.[PMID: 28631728 DOI: 10.1038/ajg.2017.154]
Ford AC, Luthra P, Tack J, et al. Efficacy of psychotropic drugs in functional dyspepsia: systematic review and meta-analysis. Gut.2017;66(3):411-420.[PMID: 26567029 DOI: 10.1136/gutjnl-2015-310721]
Masuy I, Van Oudenhove L, Tack J. Review article: treatment options for functional dyspepsia. Aliment Pharmacol Ther.2019;49(9):1134-1172.[PMID: 30924176 DOI: 10.1111/apt.15191]
Aranow C, Atish-Fregoso Y, Lesser M, et al. Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial. Ann Rheum Dis.2021;80(2):203-208.[PMID: 33144299 DOI: 10.1136/annrheumdis-2020-217872]
Zhu Y, Xu F, Lu DW, et al. Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia by enhancing vagal efferent activity. Am J Physiol Gastrointest Liver Physiol.2021;320(5):G700-G711.[PMID: 33624527 DOI: 10.1152/ajpgi.00426.2020]
Frøkjaer JB, Bergmann S, Brock C, et al. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. Neurogastroenterol Motil.2016;28(4):592-598.[PMID: 26728182 DOI: 10.1111/nmo.12760]
Mercante B, Ginatempo F, Manca A, et al. Anatomo-Physiologic Basis for Auricular Stimulation. Med Acupunct .2018;30(3):141-150.[PMID: 29937968 DOI: 10.1089/acu.2017.1254]
He W, Jing XH, Zhu B, et al. The auriculo-vagal afferent pathway and its role in seizure suppression in rats. BMC Neurosci.2013;14:85.[PMID: 23927528 DOI: 10.1186/1471-2202-14-85]
Liu LS, Winston JH, Shenoy MM, et al. A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation. Gastroenterology.2008;134(7):2070-2079.[PMID: 18448102 DOI: 10.1053/j.gastro.2008.02.093]
Zhang S, Li S, Liu Y, et al. Electroacupuncture via chronically implanted electrodes improves gastric dysmotility mediated by autonomic-cholinergic mechanisms in a rodent model of functional dyspepsia. Neurogastroenterol Motil.2018;30(10):e13381.[PMID: 29856090 DOI: 10.1111/nmo.13381]
Zhou J, Li S, Wang Y, et al. Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia. PLoS One.2017;12(3):e0174568.[PMID: 28350818 DOI: 10.1371/journal.pone.0174568]
Nishio H, Hayashi Y, Terashima S, et al. Role of endogenous nitric oxide in mucosal defense of inflamed rat stomach following iodoacetamide treatment. Life Sci.2006;79(16):1523-1530.[PMID: 16730029 DOI: 10.1016/j.lfs.2006.04.013]
Liu L, Li Q, Sapolsky R, et al. Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults. PLoS One.2011;6(5):e19498.[PMID: 21589865 DOI: 10.1371/journal.pone.0019498]
Kewan A, Saneyasu T, Kamisoyama H, et al. Effects of fasting and re-feeding on the expression of CCK, PYY, hypothalamic neuropeptides, and IGF-related genes in layer and broiler chicks. Comp Biochem Physiol A Mol Integr Physiol .2021;257:110940.[PMID: 33785435 DOI: 10.1016/j.cbpa.2021.110940]
Singh R, Mittal B, Ghoshal UC. Functional dyspepsia is associated with GNβ3 C825T and CCK-AR T/C polymorphism. Eur J Gastroenterol Hepatol.2016;28(2):226-232.[PMID: 26551933 DOI: 10.1097/MEG.0000000000000511]
Parkman HP, Camilleri M, Farrugia G, et al. Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS meeting. Neurogastroenterol Motil.2010;22(2):113-133.[PMID: 20003077 DOI: 10.1111/j.1365-2982.2009.01434.x]
Zhao X, Wang H, Zhang Z, et al. Effects of ethyl acetate extract of Salsola collina on brain-gut peptides and interstitial cells of gastric Cajal in rats with diabetic gastroparesis. Salsola collina.2020;23(9):1218-1224.[PMID: 32963744 DOI: 10.22038/ijbms.2020.43521.10223]
Wu GJ, Cai XD, Xing J, et al. Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease. Am J Physiol Regul Integr Comp Physiol.2017;313(2):R149-R157.[PMID: 28566304 DOI: 10.1152/ajpregu.00317.2016]
Tang L, Zeng Y, Li L, et al. Electroacupuncture Upregulated Ghrelin in Rats with Functional Dyspepsia via AMPK/TSC2/Rheb-Mediated mTOR Inhibition. Dig Dis Sci.2020;65(6):1689-1699.[PMID: 31863340 DOI: 10.1007/s10620-019-05960-5]
Wilder-Smith CH. The balancing act: endogenous modulation of pain in functional gastrointestinal disorders. Gut.2011;60(11):1589-1599.[PMID: 21768212 DOI: 10.1136/gutjnl-2011-300253]
Xuan JL, Zhu YW, Xu WH, et al. Integrative effects of transcutaneous electrical acustimulation on abdominal pain, gastrointestinal motility, and inflammation in patients with early-stage acute pancreatitis. Neurogastroenterol Motil.2022;34(4):e14249.[PMID: 34536258 DOI: 10.1111/nmo.14249]
Weng RX, Chen W, Tang JN, et al. Targeting spinal TRAF6 expression attenuates chronic visceral pain in adult rats with neonatal colonic inflammation. Mol Pain.2020;16:1744806920918059.[PMID: 32299285 DOI: 10.1177/1744806920918059]
Zhao YX, He W, Jing XH, et al. Transcutaneous auricular vagus nerve stimulation protects endotoxemic rat from lipopolysaccharide-induced inflammation. Evid Based Complement Alternat Med.2012;2012:627023.[PMID: 23346208 DOI: 10.1155/2012/627023]
Teng W, Chen H, Guo F, et al. Expression and distribution of SP and its NK1 receptor in the brain-gut axis in neonatal maternally separated rat model with visceral hypersensitivity. Genet Mol Res .2016;15(3):10.[PMID: 27706667 DOI: 10.4238/gmr.15038999]
Yin Y, Zhong L, Wang JW, et al. Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P. World J Gastroenterol.2015;21(15):4536-4546.[PMID: 25914462 DOI: 10.3748/wjg.v21.i15.4536]
Hou LW, Rong PJ, Li L, et al. [Effects of transcutaneous auricular vagus nerve stimulation on autonomic nervous function in rats with functional dyspepsia]. Zhen Ci Yan Jiu 2021;46:663–670.
Tracey KJ. The inflammatory reflex. Nature.2002;420(6917):853-859.[PMID: 12490958 DOI: 10.1038/nature01321]
Van Den Houte K, Carbone F, Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol.2019;13(1):37-46.[PMID: 30791841 DOI: 10.1080/17474124.2019.1543586]
Talley NJ. Functional dyspepsia: new insights into pathogenesis and therapy. Korean J Intern Med.2016;31(3):444-456.[PMID: 27048251 DOI: 10.3904/kjim.2016.091]
Taki M, Oshima T, Li M, et al. Duodenal low-grade inflammation and expression of tight junction proteins in functional dyspepsia. Neurogastroenterol Motil.2019;31(10):e13576.[PMID: 30790378 DOI: 10.1111/nmo.13576]
Wauters L, Burns G, Ceulemans M, et al. Duodenal inflammation: an emerging target for functional dyspepsia?Expert Opin Ther Targets.2020;24(6):511-523.[PMID: 32249629 DOI: 10.1080/14728222.2020.1752181]
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