title: HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model.
abstract: OBJECTIVE
  Hypoesthesia is a clinical feature of neuropathic pain. The feature is partly explained by the evidence of epigenetic repression of Nav 1.8 sodium channel in the dorsal root ganglion (DRG).
  
  
  METHODS
  We investigated the possibility of trichostatin A (TSA), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to reverse the unique C-fibre sensitivity observed following partial ligation of sciatic nerve in mice.
  
  
  RESULTS
  Nerve injury-induced down-regulation of DRG Nav 1.8 sodium channel and C-fibre-related hypoesthesia were reversed by TSA, VPA and SAHA treatments, which inhibit histone deacetylase (HDAC), and increase histone acetylation at the regulatory sequence of Nav 1.8.
  
  
  CONCLUSIONS
  Taken together, these studies provide the evidence that hypoesthesia and underlying down-regulation of Nav 1.8, negative symptoms observed in nerve injury-induced neuropathic pain models are regulated by an epigenetic chromatin remodelling through HDAC-related machineries.
authors.affiliation: Department of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Kohei
authors.initials: K
authors.lastname: Araki
authors.forename: Olaposi idowu
authors.initials: Oi
authors.lastname: Omotuyi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Mukae
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000107:Acetylation; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D006987:Hypesthesia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000201:enzymology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D012584:Sciatic Nerve / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D000700:Analgesics; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; C012589:trichostatin A; D000077337:Vorinostat; D014635:Valproic Acid; D006655:Histone Deacetylases
keywords: HDAC inhibitor; Nav1.8; epigenetics; hypoesthesia; neuropathic pain
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