Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via alpha 2-Adrenoceptors in Trigeminal Ganglion Neurons

Abstract

Dexmedetomidine, an alpha 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 v 1.7 and Na v 1.8, as well as alpha 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-Na) via alpha 2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of I-Na in small-sized TG neurons. I-Na inhibition by dexmedetomidine was blocked by yohimbine, a competitive alpha 2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of I-Na was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDP beta-S. Our results suggest that the I-Na inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled alpha 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.