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This study was designed to investigate the effects and mechanisms of GES for visceral hypersensitivity in a rodent model of functional dyspepsia (FD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Sprague\u2010Dawley rat pups at 10\u2010days old received 0.1% iodoacetamide (IA) daily for 6\u00a0days. The experiments were performed when the rats reached 8\u201011\u00a0weeks of age, and visceral hypersensitivity was established. Then, GES parameters were optimized and the chronic effects of GES on gastric hypersensitivity were assessed by electromyogram (EMG). Naloxone (3\u00a0mg\/kg), D\u2010Phe\u2010Cys\u2010Tyr\u2010D\u2010Trp\u2010Orn\u2010Thr\u2010Pen\u2010Thr\u2010NH2 (CTOP, 1\u00a0mg\/kg), and anti\u2010NGF (16\u00a0\u03bcg\/kg) were individually intraperitoneally injected to investigate opioid and nerve growth factor (NGF) mechanisms. Tissues were analyzed for NGF expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In the IA\u2010treated rats, the visceromotor response to gastric distension was significantly increased, and both acute GES with optimized stimulation parameters (0.25\u00a0seconds on, 0.25\u00a0seconds off, 100\u00a0Hz, 0.25\u00a0ms, 6\u00a0mA) and chronic GES (7\u00a0days, 2 hours\/day) normalized gastric hypersensitivity. The inhibitory effect of GES on gastric hypersensitivity was blocked by naloxone and CTOP. Anti\u2010NGF normalized EMG responses in IA\u2010treated rats. The expressions of NGF in the tissues of IA\u2010treated rats were dramatically increased, and these increases were suppressed with GES.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>GES with optimized parameters improves gastric hypersensitivity induced by neonatal treatment of IA mediated peripherally by suppressing NGF and via the opioid mechanism involving the \u00b5 receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13551","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T06:19:17Z","timestamp":1550729957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-9343","authenticated-orcid":false,"given":"Yan","family":"Dong","sequence":"first","affiliation":[{"name":"Veterans Research and Education Foundation VA Medical Center Oklahoma City Oklahoma"},{"name":"Institute of Chinese Traditional Surgery, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Li","sequence":"additional","affiliation":[{"name":"Veterans Research and Education Foundation VA Medical Center Oklahoma City Oklahoma"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyun","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiande D. 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