Eugenol Inhibits ATP-induced P2X Currents in Trigeminal Ganglion Neurons

  • Li, Hai Ying (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Lee, Byung-Ky (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kim, Joong-Soo (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Jung, Sung-Jun (Department of Physiology, College of Medicine, Kangwon National University) ;
  • Oh, Seog-Bae (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University)
  • Published : 2008.12.31

Abstract

Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated $Na^+$ and $Ca^{2+}$ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on $P2X_3$, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and $Ca^{2+}$ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and $P2X_3$-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and $\alpha$, $\beta$-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that $P2X_3$ mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only $Ca^{2+}$ transients evoked by $\alpha$, $\beta$-meATP, the selective $P2X_3$ agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in $P2X_3$-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits $P2X_3$ currents in a TRPV1-independent manner, which contributes to its analgesic effect.

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