J Neurogastroenterol Motil.  2017 Jul;23(3):464-476. 10.5056/jnm16161.

Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach

• Li M
• Xue L
• Zhu HY
• Wang H
• Xu X
• Zhang PA
• Wu G
• Xu GY

• KMID: 2387838
• DOI: http://doi.org/10.5056/jnm16161

Abstract

BACKGROUND/AIMS
Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. 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 induced 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.
CONCLUSIONS
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.

Keyword

Corticosterone; Ganglia; spinal; Protein kinase C; Visceral pain; Voltage-gated sodium channel

MeSH Terms

Abdominal Pain
Action Potentials
Animals
Corticosterone
Cyclic AMP-Dependent Protein Kinases
Diagnosis-Related Groups
Dyspepsia
Ganglia
Ganglia, Spinal*
Humans
Hypersensitivity
Injections, Intraperitoneal
Neck Muscles
Neurons
Protein Kinase C*
Protein Kinases*
Rats*
Sodium
Sodium Channels
Spinal Nerve Roots*
Stomach*
Visceral Pain
Corticosterone
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Protein Kinases
Sodium
Sodium Channels