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 Ca(2+) channels, NMDA receptor and GABA(A) 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 K(d) values were 308 muM and 543 muM, 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.
Cho
Jeong Seon
JS
Department of Pharmacology, College of Medicine, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, Republic of Korea.
Kim
Tae Hoon
TH
Lim
Jae-Min
JM
Song
Jin-Ho
JH
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000700:Analgesics; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005054:Eugenol; D013779:Tetrodotoxin