Epigenetic mechanisms are involved in
epilepsy and
chronic pain development. About that, we studied the effects of the natural
histone deacetylase (
HDAC) inhibitor sodium butyrate (BUT) in comparison with
valproic acid (VPA) in a validated genetic model of generalized
absence epilepsy and epileptogenesis. WAG/Rij rats were treated with BUT (30 mg/kg), VPA (300 mg/kg), and their combination (BUT + VPA) daily per os for 6 months. Rats were subjected at Randall-Selitto, von Frey, hot plate, and tail flick tests after 1, 3, and 6 months of treatment to evaluate
hypersensitivity to noxious and non-noxiuous stimuli. Moreover,
PPAR-γ (G3335 1 mg/kg),
GABA-B (CGP35348 80 mg/kg), and
opioid (
naloxone 1 mg/kg) receptor antagonists were administrated to investigate the possible mechanisms involved in
analgesic activity. The expression of NFkB,
glutathione reductase, and
protein oxidation (carbonylation) was also evaluated by Western blot analysis. WAG/Rij rats showed an altered pain threshold throughout the study (p < 0.001). BUT and BUT + VPA treatment reduced
hypersensitivity (p < 0.01). VPA was significantly effective only after 1 month (p < 0.01). All the three receptors are involved in BUT + VPA effects (p < 0.001). BUT and BUT + VPA decreased the expression of NFkB and enhanced
glutathione reductase (p < 0.01);
protein oxidation (carbonylation) was reduced (p < 0.01). No effect was reported with VPA. In conclusion BUT, alone or in coadministration with VPA, is a valuable candidate for managing the
epilepsy-related persistent
pain.