HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model.
Br J Pharmacol
; 170(5): 991-8, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24032674
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). EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nervo Isquiático
/
Limiar da Dor
/
Neuropatia Ciática
/
Fibras Nervosas Amielínicas
/
Inibidores de Histona Desacetilases
/
Histona Desacetilases
/
Analgésicos
/
Hipestesia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão