E-GEOD-51294 - HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain [spinal cord tissue]
Released on 1 October 2013, last updated on 7 October 2013
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. n = 4, HDACi treated vs. vehicle treated. Ipsilateral dorsal spinal cord tissue after L5 spinal nerve transection, DRG tissue was run in a separate Affymetrix experiment.
transcription profiling by array
Franziska Denk <firstname.lastname@example.org>, A Bithell, A S Rice, B Sidders, D Ziemek, F Denk, J Grist, M Crow, N J Buckely, S B McMahon, S Sharma, W Huang
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 AS, Buckley NJ, McMahon SB. , Europe PMC 23693161