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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 publication

DOI

10.1016/j.pain.2013.05.021

Type

Journal article

Journal

Pain

Publication Date

09/2013

Volume

154

Pages

1668 - 1679

Keywords

Histone deacetylase, Histone deacetylase inhibitors, Neuropathic pain, Animals, Anti-Retroviral Agents, Benzamides, Disease Models, Animal, Dose-Response Relationship, Drug, Histone Deacetylase Inhibitors, Hyperalgesia, Male, Neuralgia, Pain Measurement, Pyridines, Pyrimidines, Rats, Rats, Wistar, Time Factors