# PubMed- Neonatal colonic inflammation sensitizes voltage-gated sodium channels via upregulation of cystathionine Î²-synthetase expression in rat prima



## VSsupport (Feb 12, 2008)

[TD]
*Neonatal colonic inflammation sensitizes voltage-gated sodium channels via upregulation of cystathionine Î²-synthetase expression in rat primary sensory neurons.*

Am J Physiol Gastrointest Liver Physiol. 2013 Feb 28;

Authors: Qu R, Tao J, Wang Y, Zhou Y, Wu G, Xiao Y, Hu CY, Jiang X, Xu GY

Abstract
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 sodium channel activities and roles for endogenous hydrogen sulfide producing enzyme cystathionine Î²-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded CRD in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with DiI and acutely dissociated for measuring sodium channel currents. Western blot analysis was employed to detect changes in expressions of Nav1.7, Nav1.8 and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to a ~2.5 fold increase in sodium current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Nav1.7, NaV1.8 and CBS in colon related DRGs. CBS was colocalized with NaV1.7 or 1.8 in colon-specific DRG neurons. Administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed sodium current density and reduced expression of Nav1.7 and NaV1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats, in a dose-dependent manner. These data suggest that NCI enhances sodium channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.

PMID: 23449670 [PubMed - as supplied by publisher]

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