title: Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation.
abstract: BACKGROUND
  Irritable 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.
  
  
  RESULTS
  CVH 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 7th to 12th 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital, Soochow University, Suzhou 215123, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Ruihua
authors.initials: R
authors.lastname: Xie
authors.forename: Shufen
authors.initials: S
authors.lastname: Hu
authors.forename: Yongmeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.forename: Xinghong
authors.initials: X
authors.lastname: Jiang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Chuang-Ying
authors.initials: CY
authors.lastname: Hu
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000235:genetics / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D051381:Rats; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D059265:Visceral Pain / Q000235:genetics / Q000378:metabolism*
chemical_list: C498145:Rela protein, rat; D051996:Transcription Factor RelA; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide