Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via <i>α</i> 2-Adrenoceptors in Trigeminal Ganglion Neurons

다국어 초록 (Multilingual Abstract)

<P>Dexmedetomidine, an <I>α</I>2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Na<SUB>v</SUB>1.7 and Na<SUB>v</SUB>1.8, as well as <I>α</I>2-adrenoceptors are expressed in primary sensory neurons of the trigeminal ganglion (TG). Using whole-cell patch-clamp recordings, we investigated the effects of dexmedetomidine on voltage-gated sodium channel currents (<I>I</I><SUB>Na</SUB>) via <I>α</I>2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of <I>I</I><SUB>Na</SUB> in small-sized TG neurons. <I>I</I><SUB>Na</SUB> inhibition by dexmedetomidine was blocked by yohimbine, a competitive <I>α</I>2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of <I>I</I><SUB>Na</SUB> was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDP<I>β</I>-S. Our results suggest that the <I>I</I><SUB>Na</SUB> inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled <I>α</I>2-adrenoceptors, might contribute to the analgesic effects of dexmedetomidine in the trigeminal system. Therefore, these new findings highlight a potential novel target for analgesic drugs in the orofacial region.</P>