Protein Kinase C Mediates The Corticosterone-induced Sensitization Of Dorsal Root Ganglion Neurons Innervating The Rat Stomach

Background: Gastric hypersensitivity contributes to epigastric 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 this 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 Di I injection into the stomach wall.Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents.Electromyograph techniques were used to determine the responses of neck muscles to gastric distention(GD).Results: Under whole-cell mode,Incubation of acutely isolated DRG neurons with CORT significantly increased excitability of DRG neurons and enhanced voltage-gated sodium current density.Pre-incubation of GF109203 X,an inhibitor of protein kinase C(PKC),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 GF109203 X 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 PKC but not PKA signaling pathway in DRG neurons innervating the stomach,thus underlying the gastric hypersensitivity induced by CORT injection.