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

Abstract

SummaryIntrathecal delivery of histone deacetylase inhibitors ameliorates hypersensitivity in models of neuropathic pain. This effect may be mediated at the level of the spinal cord through inhibition of HDAC1 function.

Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain?

“…The interactions between HATs and HDACs determine the net balance of histone acetylation (Binder et al, 2013). Mounting evidence suggests that during pain-related synaptic plasticity, the expression and activities of HDACs are dynamic (Geranton and Tochiki, 2015;Cherng et al, 2014;Matsushita et al, 2013;Kiguchi et al, 2013;Denk et al, 2013). Therefore, in the present review, we focus on mechanisms of histone acetylation and the role of HDACs in chronic pain and discuss recent attempts to treat chronic pain with HDAC inhibitors (HDACIs).…”

“…Increasing attention has been paid to the development of both non-selective and selective HDAC inhibitors (Abel and Zukin, 2008;Bai et al, 2010;Denk et al, 2013;Descalzi et al, 2015;Geranton and Tochiki, 2015;Grayson et al, 2010;Micelli and Rastelli, 2015). Many HDACIs are currently being studied in clinical trials or have even been or approved by the US Food and Drug Administration (FDA) for the treatment of cancers (Chung et al, 2003;Dekker et al, 2014;Niesvizky et al, 2011).…”

Circulating microRNA Signatures in Rodent Models of Pain

“…Chemotherapy-induced peripheral neuropathic pain is a severe adverse effect observed in 30 to 80 % of patients during and after treatment [48,49]. HDAC inhibitors are chemotherapy drugs that can alleviate [50][51][52] or induce pain [32,53,54] depending on the compound, rodent model studied, and treatment regimen used. The primary function attributed to HDAC inhibitors is to increase acetylation of histones, resulting in increased transcriptional accessibility.…”

Targeting Selective Autophagy of Insoluble Protein Aggregates

“…Class I-selective HDAC inhibitors for non-oncology indications [94,95]-and neurodegeneration in particular [96,97]-are supported by a scientific rationale. Even focused inhibition of class I HDACs, though, leads to sub-optimal toxicity profiles that should be acceptable only in acute, oncology-like indications [98].…”