Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity

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Abstract

Background: Gastric 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). Methods: Male 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 Results: In 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 Inferences: 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 µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.

Original languageEnglish (US)
Article numbere13551
JournalNeurogastroenterology and Motility
Volume31
Issue number5
DOIs
StatePublished - May 1 2019

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Nerve Growth Factor
Opioid Analgesics
Electric Stimulation
Rodentia
Stomach
Hypersensitivity
Iodoacetamide
Electromyography
Naloxone
Visceral Pain
Dyspepsia
Sprague Dawley Rats

Keywords

  • functional dyspepsia
  • gastric electrical stimulation
  • nerve growth factor
  • opioid pathway
  • visceral hypersensitivity

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

@article{989d06757bab4932868ac162d9138c2b,
title = "Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity",
abstract = "Background: Gastric 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). Methods: Male 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 Results: In 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 Inferences: 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 µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.",
keywords = "functional dyspepsia, gastric electrical stimulation, nerve growth factor, opioid pathway, visceral hypersensitivity",
author = "Yan Dong and Shiying Li and Jieyun Yin and Jiande Chen",
year = "2019",
month = "5",
day = "1",
doi = "10.1111/nmo.13551",
language = "English (US)",
volume = "31",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
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TY - JOUR

T1 - Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity

AU - Dong, Yan

AU - Li, Shiying

AU - Yin, Jieyun

AU - Chen, Jiande

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background: Gastric 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). Methods: Male 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 Results: In 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 Inferences: 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 µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.

AB - Background: Gastric 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). Methods: Male 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 Results: In 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 Inferences: 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 µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.

KW - functional dyspepsia

KW - gastric electrical stimulation

KW - nerve growth factor

KW - opioid pathway

KW - visceral hypersensitivity

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