Neonatal colonic inflammation sensitizes voltage-gated Na+ channels via upregulation of cystathionine β-synthetase expression in rat primary sensory neurons

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na+ channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded colorectal distention in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with 1,1′-dioleyl-3,3,3′,3-tetramethylindocarbocyanine methanesulfonate and acutely dissociated for measuring Na+ channel currents. Western blot analysis was employed to detect changes in expressions of voltage-gated Na+ (NaV) channel subtype 1.7, NaV1.8, and CBS. NCI significantly increased AWR scores when compared w...