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

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 Ca2+ channels, NMDA receptor and GABAA 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 Kd 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.