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.
© 2013 The British Pharmacological Society.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Analgesics / pharmacology*
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Animals
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Chromatin Assembly and Disassembly / drug effects
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Disease Models, Animal
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Epigenesis, Genetic / drug effects
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / enzymology
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Ganglia, Spinal / physiopathology
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Histone Deacetylase Inhibitors / pharmacology*
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Histone Deacetylases / metabolism*
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Histones / metabolism
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Hydroxamic Acids / pharmacology
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Hypesthesia / drug therapy*
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Hypesthesia / enzymology
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Hypesthesia / genetics
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Hypesthesia / physiopathology
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Ligation
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Male
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Mice
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Mice, Inbred C57BL
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NAV1.8 Voltage-Gated Sodium Channel / drug effects
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NAV1.8 Voltage-Gated Sodium Channel / genetics
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NAV1.8 Voltage-Gated Sodium Channel / metabolism
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Nerve Fibers, Unmyelinated / drug effects*
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Nerve Fibers, Unmyelinated / enzymology
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Pain Measurement
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Pain Threshold / drug effects*
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Sciatic Nerve / drug effects*
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Sciatic Nerve / physiopathology
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Sciatic Nerve / surgery
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Sciatic Neuropathy / drug therapy*
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Sciatic Neuropathy / enzymology
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Sciatic Neuropathy / genetics
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Sciatic Neuropathy / physiopathology
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Time Factors
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Valproic Acid / pharmacology
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Vorinostat
Substances
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Analgesics
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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NAV1.8 Voltage-Gated Sodium Channel
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Scn10a protein, mouse
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trichostatin A
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Vorinostat
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Valproic Acid
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Histone Deacetylases