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

Dexmedetomidine, an α 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, Nav 1.7 and Nav 1.8, as well as α 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 α 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 α 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 β -S. Our results suggest that the I Na inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled α 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.