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Author (up) Denk, F.; Huang, W.; Sidders, B.; Bithell, A.; Crow, M.; Grist, J.; Sharma, S.; Ziemek, D.; Rice, A.S.; Buckley, N.J.; McMahon, S.B.
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  Title HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain Type Journal Article
  Year 2013 Publication Pain Abbreviated Journal Pain  
  Volume Issue Pages  
  Keywords  
  Abstract Histone deacetylase inhibitors (HDACi) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain [1-3]. This study set out to determine whether these compounds could also impact neuropathic pain. Different class I HDACi were delivered intrathecally to rat spinal cord in models of traumatic nerve injury and antiretroviral drug induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40-50% as a result of HDACi treatment, but only if commenced prior to any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia (DRG) in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence and/or maintenance of neuropathic pain.  
  Address King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London SE1 1UL.. Electronic address: franziska.denk@kcl.ac.uk  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0304-3959 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23693161 Approved no  
  Call Number @ @ Serial 39811  
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