Eugenol inhibits sodium currents in dental afferent neurons

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.