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HDAC inhibitors restore C ‐fibre sensitivity in experimental neuropathic pain model
Author(s) -
Matsushita Yosuke,
Araki Kohei,
Omotuyi Olaposi idowu,
Mukae Takehiro,
Ueda Hiroshi
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12366
Subject(s) - hypoesthesia , neuropathic pain , trichostatin a , histone deacetylase , chemistry , dorsal root ganglion , pharmacology , nociception , hypoalgesia , histone , sodium channel , nerve injury , hyperalgesia , medicine , anesthesia , biochemistry , neuroscience , biology , sodium , receptor , spinal cord , gene , organic chemistry
Background and Purpose Hypoesthesia is a clinical feature of neuropathic pain. The feature is partly explained by the evidence of epigenetic repression of Na v 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 Na v 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 Na v 1.8. Conclusions and Implications Taken together, these studies provide the evidence that hypoesthesia and underlying down‐regulation of Na v 1.8, negative symptoms observed in nerve injury‐induced neuropathic pain models are regulated by an epigenetic chromatin remodelling through HDAC ‐related machineries.