Eugenol is widely used in dentistry as a local
analgesic agent, because of its ability to allay tooth
pain. Interestingly,
eugenol shares several pharmacological actions with
local anesthetics which include inhibition of
voltage-gated sodium channel (VGSC) and activation of transient receptor potential vanilloid subtype 1 (TRPV1). In the present study, we investigated the effects of
eugenol on
pain behaviors in orofacial area, and as an attempt to elucidate its mechanism we characterized inhibitory effects of
eugenol on VGSCs in trigeminal ganglion (TG) neurons. TG neurons were classified into four types on the basis of their neurochemical and electrophysiological properties such as cell size, shapes of action potential (AP), isolectin-B(4) (IB(4)) binding, and were analyzed for the association of their distinctive electrophysiological properties and
mRNA expression of Na(v)1.8 and TRPV1 by using single-cell RT-PCR following whole-cell recordings.
Subcutaneous injection of
eugenol reduced the thermal nociception and
capsaicin-induced
thermal hyperalgesia in a dose-dependent manner.
Eugenol also diminished digastric electromyogram evoked by noxious electrical stimulation to anterior tooth pulp, which was attributable to the blockade of AP conduction on inferior alveolar nerve. At cellular level,
eugenol reversibly inhibited APs and VGSCs in IB(4)+/TRPV1+/Na(v)1.8+ nociceptive TG neurons (Type I-Type III) and IB(4)-/TRPV1-/Na(v)1.8- nociceptive TG neurons (Type IV). Both TTX-resistant I(Na) in Type I-Type III neurons and TTX-sensitive I(Na) in Type IV neurons were sensitive to
eugenol. Taken together, these results suggest that
eugenol may serve as
local anesthetics for other pathological
pain conditions in addition to its wide use in dental clinic.