Effects of eugenol on Na + currents in rat dorsal root ganglion neurons

Abstract

Eugenol is an aromatic molecule found in several plants and widely used in dentistry for analgesic and antiseptic purposes. It inhibits pro-inflammatory mediators including nitric oxide synthase, cyclooxygenase and lipoxygenase. It also regulates ion channels involved in pain signaling, such as TRPV1 receptor, high-voltage-activated Ca 2+ channels, NMDA receptor and GABA A receptor. The expression and functional properties of voltage-gated Na + channels in primary sensory neurons are altered following inflammation or nerve injury. To elucidate an involvement of Na + channels in the eugenol-induced analgesia we investigated the effects of eugenol on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na + currents in acutely dissociated rat dorsal root ganglion neurons. Eugenol inhibited TTX-S and TTX-R Na + currents in a concentration-dependent manner. The K d values were 308 μM and 543 μM, respectively. Eugenol did not influence the activation voltage of either type of Na + current. However, eugenol moved the steady-state inactivation curves of both Na + currents to a hyperpolarizing direction and reduced the maximal Na + current. Thus eugenol appears to inhibit Na + currents through its interaction with both resting and inactivated Na + channels. The recovery from inactivation of both Na + currents was slowed by eugenol. The eugenol inhibition of Na + currents was not dependent on the stimulus frequency. The inhibition of Na + currents is considered as one of the mechanisms by which eugenol exerts analgesia.