J Neurogastroenterol Motil  
Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach
Meng LI, Lu Xue, Hong-Yan Zhu, Hongjun Wang, Xue Xu, Geping Wu, Guang-Yin Xu*
The Affiliated Zhangjiagan Hospital of Soochow University, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, P.R. China.
Correspondence to: Guang-Yin Xu, MD, PhD
Laboratory of Translational Pain Medicine, Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China
Tel: +86-512-6588-2817, Fax: +86-512-6588-3602, E-mail: guangyinxu@suda.edu.cn
Received: September 21, 2016; Revised: December 31, 2016; Accepted: January 15, 2017; Published online: March 26, 2017.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia (FD). Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach.
Methods DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension.
Results Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials iinduced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89.
Conclusion Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.
Keywords: Corticosterone, Ganglia, spinal, Protein kinase C, Visceral pain, Voltage-gated sodium channel


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