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Br J Pharmacol. 2013 Nov;170(5):991-8. doi: 10.1111/bph.12366.

HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model.

Author information

1
Department of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Abstract

BACKGROUND AND PURPOSE:

Hypoesthesia is a clinical feature of neuropathic pain. The feature is partly explained by the evidence of epigenetic repression of Nav 1.8 sodium channel in the dorsal root ganglion (DRG).

EXPERIMENTAL APPROACH:

We investigated the possibility of trichostatin A (TSA), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to reverse the unique C-fibre sensitivity observed following partial ligation of sciatic nerve in mice.

KEY RESULTS:

Nerve injury-induced down-regulation of DRG Nav 1.8 sodium channel and C-fibre-related hypoesthesia were reversed by TSA, VPA and SAHA treatments, which inhibit histone deacetylase (HDAC), and increase histone acetylation at the regulatory sequence of Nav 1.8.

CONCLUSIONS AND IMPLICATIONS:

Taken together, these studies provide the evidence that hypoesthesia and underlying down-regulation of Nav 1.8, negative symptoms observed in nerve injury-induced neuropathic pain models are regulated by an epigenetic chromatin remodelling through HDAC-related machineries.

KEYWORDS:

HDAC inhibitor; Nav1.8; epigenetics; hypoesthesia; neuropathic pain

PMID:
24032674
PMCID:
PMC3949648
DOI:
10.1111/bph.12366
[Indexed for MEDLINE]
Free PMC Article

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