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

Denk, F., Huang, W., Sidders, B., Bithell, A., Crow, M., Grist, J., Sharma, S., Ziemek, D., Rice, A. S.C., Buckley, N. J. and McMahon, S. B. (2013) HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain. Pain, 154 (9). pp. 1668-1679. ISSN 0304-3959

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To link to this item DOI: 10.1016/j.pain.2013.05.021

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:34702
Uncontrolled Keywords:Histone deacetylase; Histone deacetylase inhibitors; Neuropathic pain
Publisher:Elsevier

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