Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivationReport as inadecuate




Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 8:89

First Online: 18 December 2012Received: 14 November 2012Accepted: 12 December 2012

Abstract

BackgroundIrritable bowel syndrome IBS is characterized by chronic visceral hyperalgesia CVH that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide H2S producing enzyme cystathionine beta-synthetase CBS and p65 nuclear factor-kappa B subunits in CVH.

ResultsCVH was induced by neonatal maternal deprivation NMD in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7 to 12 week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention CRD, an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD.

ConclusionThe present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.

KeywordsDorsal root ganglion Neonatal maternal deprivation Chronic visceral pain Hydrogen sulfide Nuclear factor kappa B AbbreviationsAOAAO-Carboxymethyl hydroxylamine hemihydrochloride

AWRAbdoninal withdrawal reflex

CRDColorectal distention

CVHChronic visceral hyperalgesia

DTDistention threshold

H2SHydrogen sulfide

IBSIrritable bowel syndrome

NF-kBNuclear factor kappa B

NMDNeonatal maternal deprivation

PDTCPyrrolidine dithiocarbamate.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-89 contains supplementary material, which is available to authorized users.

Lin Li, Ruihua Xie contributed equally to this work.

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Author: Lin Li - Ruihua Xie - Shufen Hu - Yongmeng Wang - Tianzhu Yu - Ying Xiao - Xinghong Jiang - Jianguo Gu - Chuang-Ying Hu -

Source: https://link.springer.com/



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