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Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity.
Neurogastroenterol Motil 2019; 31(5):e13551NM

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.

Authors+Show Affiliations

Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, Oklahoma. Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, Oklahoma. Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30790401

Citation

Dong, Yan, et al. "Ameliorating Effects of Optimized Gastric Electrical Stimulation and Mechanisms Involving Nerve Growth Factor and Opioids in a Rodent Model of Gastric Hypersensitivity." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 31, no. 5, 2019, pp. e13551.
Dong Y, Li S, Yin J, et al. Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity. Neurogastroenterol Motil. 2019;31(5):e13551.
Dong, Y., Li, S., Yin, J., & Chen, J. D. Z. (2019). Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 31(5), pp. e13551. doi:10.1111/nmo.13551.
Dong Y, et al. Ameliorating Effects of Optimized Gastric Electrical Stimulation and Mechanisms Involving Nerve Growth Factor and Opioids in a Rodent Model of Gastric Hypersensitivity. Neurogastroenterol Motil. 2019;31(5):e13551. PubMed PMID: 30790401.
* Article titles in AMA citation format should be in sentence-case
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 D Z, Y1 - 2019/02/20/ PY - 2018/05/02/received PY - 2018/12/09/revised PY - 2018/12/20/accepted PY - 2019/2/23/pubmed PY - 2019/2/23/medline PY - 2019/2/22/entrez KW - functional dyspepsia KW - gastric electrical stimulation KW - nerve growth factor KW - opioid pathway KW - visceral hypersensitivity SP - e13551 EP - e13551 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 31 IS - 5 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. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/30790401/Ameliorating_effects_of_optimized_gastric_electrical_stimulation_and_mechanisms_involving_nerve_growth_factor_and_opioids_in_a_rodent_model_of_gastric_hypersensitivity L2 - https://doi.org/10.1111/nmo.13551 DB - PRIME DP - Unbound Medicine ER -