Molecular mechanism for local anesthetic action of eugenol in the rat trigeminal system.
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.
National Research Laboratory for Pain, Dental Research Institute and Department of Physiology, School of Dentistry, Seoul National University, 28-2 Yeongeon-Dong, Chongno-Ku, Seoul 110-749, Republic of Korea.
Chul-Kyu
CK
Park
Kihwan
K
Kim
Sung Jun
SJ
Jung
Min Ji
MJ
Kim
Dong Kuk
DK
Ahn
Seong-Doo
SD
Hong
Joong Soo
JS
Kim
Seog Bae
SB
Oh
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000379:methods; D005054:Eugenol / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007568:Jaw / Q000187:drug effects* / Q000502:physiology; D037102:Lectins / Q000378:metabolism; D008297:Male; D008410:Masticatory Muscles / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014070:Tooth / Q000294:innervation; D012668:Trigeminal Ganglion / Q000166:cytology; D014276:Trigeminal Nerve / Q000187:drug effects*
D000779:Anesthetics, Local; D037102:Lectins; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568319:Scn10a protein, rat; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D005054:Eugenol; D013779:Tetrodotoxin; D002211:Capsaicin