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

Abstract

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_v1.7 and Na_v1.8, 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>_Na) via <i>α</i>2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of <i>I</i>_Na in small-sized TG neurons. <i>I</i>_Na inhibition by dexmedetomidine was blocked by yohimbine, a competitive <i>α</i>2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of <i>I</i>_Na 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>_Na 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.