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Background & Aims: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and bloating in association with altered bowel movements.Its pathogenesis and the underlying molecular mechanisms of visceral hyperalgesia remain elusive.This study was designed to examine changes in the excitability and alteration of voltage-gated sodium channel (VGSC) of dorsal root ganglia (DRG) neurons innervating the colon in a model of neonatal maternal deprivation (NMD)-induced chronic visceral hyperalgesia.Methods: Neonatal male rats (PND 2-15) were exposed to a 3 hour period of daily maternal separation with temperature maintained at ~32 ℃.Abdominal withdrawal reflex (AWR) scores were signed to each rat by visual observation of visceromotor response to colorectal distension (CRD) at the age of 7-15 weeks.Colon specific DRG neurons (T13~L2) were labeled with Dil and acutely dissociated for measuring excitability and changes in sodium channel current under whole-cell patch-clamp configuration.Results: NMD significantly increased the visceromoter response to CRD in adult rats compared with controls.The increased response lasted for ~6 weeks within observation time period.NMD also produced hyperexcitability of colonspecific DRG neurons.This was supported by our observations that resting potentials were more depolarized and rheobase (current stimulation threshold) was significantly lower in NMD rats than in controls.In addition,the number of action potentials evoked by 2 times rheobase current stimulation was significantly higher in NMD group than in controls.Furthermore, NMD enhanced the TTX-resistant (TTX-R) sodium current but not the TTXsensitive (TTX-S) sodium current density of colon specific DRG neurons.Compared with controls, activation curve showed a leftward shift in NMD-treated group.NMD treatment also led to a ~10mV negative shift in the V1/2 of the activation curve.Furthermore, the inactivation curve of TTX-R sodium current showed a rightward shift and the slope factor has a significant decrease in NMD-treated group.Conclusion: These data suggest that NMD treatment increases the excitability of colon specific DRG neurons by increasing TTX-R sodium current density, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS.