title: EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats.
abstract: Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome.
authors.affiliation: University of Maryland School of Dentistry.
authors.forename: Dong-Yuan
authors.initials: DY
authors.lastname: Cao
authors.affiliation: University of Maryland School of Dentistry.
authors.forename: Guang
authors.initials: G
authors.lastname: Bai
authors.affiliation: University of Maryland School of Dentistry.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Ji
authors.affiliation: University of Maryland School of DentistryUniversity of Maryland School of DentistryUniversity of Maryland School of Dentistry.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Karpowicz
authors.affiliation: University of Maryland School of DentistryUniversity of Maryland School of DentistryUniversity of Maryland School of Dentistry rtraub@umaryland.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Traub
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D013315:Stress, Psychological / Q000150:complications*; D014781:Viscera / Q000473:pathology*; D000077337:Vorinostat; D014966:Xanthenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C114624:LY 341495; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D000077337:Vorinostat