Eugenol Inhibits Sodium Currents in Dental Afferent Neurons

Abstract

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents ( I Na) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I Na in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I Na, suggesting no involvement of TRPV1. Two types of I Na, tetrodotoxin (TTX)-resistant and TTX-sensitive I Na, were inhibited by eugenol. Our results demonstrated that eugenol inhibits I Na in a TRPV1-independent manner. We suggest that I Na inhibition by eugenol contributes to its analgesic effect.

CONCENTRACIONES ANESTÉSICA DEL EUGENOL EN PECES ESCALARES (Pterophyllum scalare)

“…El efecto anestésico y analgésico del eugenol ha sido atribuido a su acción inhibitoria sobre los canales de sodio (Park et al, 2006) y calcio, especialmente los canales tipo N-calcio o High voltage activated calcium channel (HVACC), dado que bloquea la generación del potencial de acción y produce una disminución en la liberación de neurotransmisores dependientes de calcio en las terminaciones presinápticas neuronales (Lee et al, 2005). Estudios in vitro han demostrado el efecto bloqueante del eugenol sobre los receptores vaniloides (TRPV1-Transient receptor potential vanilloid 1), inhibiendo así la transmisión del dolor (Yang et al, 2003); sin embargo, Lee et al (2005) indican que la acción del eugenol no es dependiente de TRPV1.…”

Experimental study of various central nervous system effects of eugenol in mice and rats

“…[11][12][13] In addition to this, it is evident that both the calcium and sodium channels are involved in overall regulation of cellular and neuronal excitability. 14 Whether the same mechanism accounts for its other CNS effects still remains obscure.…”

Effects of Eugenol on T-type Ca2+ Channel Isoforms

“…Eugenol has been reported to inhibit multiple ion channels detected in TG neurons as follows: the IC 50 values for voltage-activated Na 1 channels, HVA Ca 21 channels, voltage-activated K 1 channels, and hyperpolarization-activated cation channels are ∼600 mM, 1 mM, 376 mM, and 157 mM, respectively (Lee et al, 2005;Park et al, 2006Park et al, , 2009Li et al, 2007;Yeon et al, 2011). Taken together with the previous findings, we suggest that T-type channels are additional molecular targets for eugenol and therefore are likely to play a part in eugenol's underlying mechanism of analgesia.…”

“…Extensive studies to unveil the painrelieving mechanism of eugenol have found that the chemical potently inhibits diverse ion channels expressed in trigeminal ganglion (TG) neurons that sense dental pain (Lee et al, 2005;Park et al, 2006;Kim et al, 2011). In particular, voltageactivated Na 1 channels and high voltage-activated (HVA) Ca 21 channels have been implicated as eugenol's molecular targets for lessening pain (Lee et al, 2005;Park et al, 2006).…”

“…Extensive studies to unveil the painrelieving mechanism of eugenol have found that the chemical potently inhibits diverse ion channels expressed in trigeminal ganglion (TG) neurons that sense dental pain (Lee et al, 2005;Park et al, 2006;Kim et al, 2011). In particular, voltageactivated Na 1 channels and high voltage-activated (HVA) Ca 21 channels have been implicated as eugenol's molecular targets for lessening pain (Lee et al, 2005;Park et al, 2006). In addition to those ion channels, low-voltage-activated (LVA) T-type channel currents in TG neurons have been detected by electrophysiological recordings (Borgland et al, 2001(Borgland et al, , 2002Ikeda and Matsumoto, 2003;Ross et al, 2009).…”