• Yan Dong, Shiying Li, Jieyun Yin, and Chen Jiande D Z JDZ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland..
• Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, Oklahoma.
• Neurogastroenterol. Motil. 2019 May 1; 31 (5): e13551.

BackgroundGastric electrical stimulation (GES) has been applied to treat gastric motility disorders for decades. This study was designed to investigate the effects and mechanisms of GES for visceral hypersensitivity in a rodent model of functional dyspepsia (FD).MethodsMale Sprague-Dawley rat pups at 10-days old received 0.1% iodoacetamide (IA) daily for 6 days. The experiments were performed when the rats reached 8-11 weeks 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 mg/kg), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 1 mg/kg), and anti-NGF (16 μg/kg) were individually intraperitoneally injected to investigate opioid and nerve growth factor (NGF) mechanisms. Tissues were analyzed for NGF expression.Key ResultsIn the IA-treated rats, the visceromotor response to gastric distension was significantly increased, and both acute GES with optimized stimulation parameters (0.25 seconds on, 0.25 seconds off, 100 Hz, 0.25 ms, 6 mA) and chronic GES (7 days, 2 hours/day) normalized gastric hypersensitivity. The inhibitory effect of GES on gastric hypersensitivity was blocked by naloxone and CTOP. Anti-NGF normalized EMG responses in IA-treated rats. The expressions of NGF in the tissues of IA-treated rats were dramatically increased, and these increases were suppressed with GES.Conclusions And InferencesGES with optimized parameters improves gastric hypersensitivity induced by neonatal treatment of IA mediated peripherally by suppressing NGF and via the opioid mechanism involving the µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.© 2019 John Wiley & Sons Ltd.

22 keywords...

hide…