Co-Application of Eugenol and QX-314 Elicits the Prolonged Blockade of Voltage-Gated Sodium Channels in Nociceptive Trigeminal Ganglion Neurons.

Sung-Min Hwang,Eun Jin Go,Sang-Taek Im,Kihwan Lee,Chul-Kyu Park,Yong Ho Kim

doi:10.3390/biom10111513

Sung-Min Hwang, Eun Jin Go + Show 4 more

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https://doi.org/10.3390/biom10111513

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Abstract

Local anesthetics (LAs) can completely block nociception by inhibiting voltage-gated sodium channels (VGSCs), and thus, blocking action potentials (APs) within sensory neurons. As one of the several LAs, eugenol is used for dental pain treatment. It reportedly features multiple functions in regulating diverse ion channels. This study aimed to investigate the long-lasting analgesic effect of eugenol alone, as well as that of the combination of eugenol as a noxious-heat-sensitive transient receptor potential vanilloid 1 (TRPV1) channel agonist and a permanently charged sodium channel blocker (QX-314), on neuronal excitability in trigeminal ganglion (TG) neurons. Eugenol alone increased inward current in a dose-dependent manner in capsaicin-sensitive TG neurons. Eugenol also inhibited the VGSC current and AP. These effects were reversed through wash-out. The combination of eugenol and QX-314 was evaluated in the same manner. The combination completely inhibited the VGSC current and AP. However, these effects were not reversed and were continuously blocked even after wash-out. Taken together, our results suggest that, in contrast to the effect of eugenol alone, the combination of eugenol and QX-314 irreversibly and selectively blocked VGSCs in TG neurons expressing TRPV1.

Highlights

Recent studies on new local anesthetics (LAs) have focused on several major goals to separate sensory and motor nerve block, lengthen the duration of analgesic action, and reduce the number of side effects [1,2]
voltage-gated sodium channels (VGSCs) currents are responsible for the initial depolarization phase involved in action potentials (APs) generation, which results in pain signaling [21]
We evaluated the effect of eugenol on VGSC currents in cultured small-sized trigeminal ganglion (TG) neurons using a command pulse from a holding potential stepped from −60 to 0 mV

Summary

Introduction

Recent studies on new local anesthetics (LAs) have focused on several major goals to separate sensory and motor nerve block, lengthen the duration of analgesic action, and reduce the number of side effects [1,2]. Lidocaine action is non-selective and blocks action potentials (APs) in all sensory motor and autonomic fibers [3,4,5]. Major central nervous system and cardiovascular toxicities may occur when it is administered locally at high volumes due to the effects of lidocaine on neuronal cells and cardiac muscles [7]. A pharmacological therapy with a high selectivity for nociceptors, a longer duration of analgesia, and a reduced burden of adverse effects is needed

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