Sensitization of sodium channels by cystathionine β‐synthetase activation in colon primary sensory neurons contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation (651.20)

Abstract

Aims: This study was designed to determine roles for sodium channels and endogenous H2S signaling in a rat model of chronic visceral hypersensitivityinduced by neonatal maternal deprivation (NMD). Methods: Neonatal male rats were exposed to a 3 hour period of daily maternal separation. Colon‐specific DRG neurons were acutely dissociated for measuring excitability and sodium channel currents under whole‐cell patch clamp configurations. Expression of NaV1.8 was analyzed by western blot. Results: NMD significantly increased AWR scores. TTX‐resistant sodium current density was greatly enhanced in colon DRG neurons, activation curves showed a leftward shift in NMD rats. Furthermore, NMD remarkably enhanced expression of NaV1.8 at protein levels. AOAA, an inhibitor of CBS, significantly suppressed the expression of NaV1.8. AOAA treatment also reduced the TTX‐R sodium current density, and reversed hyperexcitability of colon‐specific DRG neurons in NMD rats. Conversely, addition of NaHS, a donor of H2S, greatly enhanced TTX‐R sodium current density, leftshifted activation curve and enhanced excitability of colon DRG neurons in age‐matched healthy rats. Conclusion: Our data suggest that NMD enhances TTX‐resistant sodium activity of colon DRG neurons, which is most likely mediated by CBS‐H2S signaling, thus contributing to chronic visceral hypersensitivity.Grant Funding Source: Supported by National Natural Science Foundation of China