HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Franziska Denk, Wenlong Huang, Ben Sidders, Angela Bithell, Megan Crow, John Grist, Simone Sharma, Daniel Ziemek, Andrew S C Rice, Noel J. Buckley, Stephen B. McMahon

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Abstract

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into 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% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia 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 of neuropathic pain.
Original languageEnglish
Pages (from-to)1668-1679
Number of pages12
JournalPain
Volume154
Issue number9
Early online date18 May 2013
DOIs
Publication statusPublished - Sep 2013

Keywords

  • histone deacetylase
  • histone deacetylase inhibitors
  • neuropathic pain

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    Denk, F., Huang, W., Sidders, B., Bithell, A., Crow, M., Grist, J., Sharma, S., Ziemek, D., Rice, A. S. C., Buckley, N. J., & McMahon, S. B. (2013). HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. Pain, 154(9), 1668-1679. https://doi.org/10.1016/j.pain.2013.05.021