Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia

Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na+ channels (Na-v) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal Na-v remain elusive. This study explores the interaction between carvacrol and Na-v in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na+ current and tetrodotoxin-resistant (TTX-R) Na+ current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na+ current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na+ current component. In addition, carvacrol-induced inhibition of TTX-R Na+ current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5 s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects Na-v gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol. (C) 2015 Elsevier B.V. All rights reserved.