Aim of investigation: To study the effect of dexmedetomidine, a selective alpha 2 adrenergic receptor (α2-AR) agonist, on tetrodotoxin (TTX)-resistant Nav1.8 current in rat DRG neurons and investigate its underlying mechanism in peripheral level.Methods: Whole-cell patch clamp recordings was used to record Nav1.8 current;Action potentials and firing rate was recorded under current clamp model;The inflammatory pain was induced by carrageenan injection to the unilateral hind paw.Results: In this study, we investigated the effect of dexmedetomidine (DEX), a selective alpha 2 adrenergic receptor, on Nav1.8, a TTX-resistant sodium channel,in rat small-diameter DRG neurons.DEX dose-dependently inhibited the Nav1.8 current in small diameter DRG neurons under both the normal and inflammatory situation, and this inhibitory effect could be partly reversed by alpha 2 adrenergic receptor antagonist Yohibine and G-protein inhibitor GDPβ-s.BRL44408, an alpha 2A adrenergic receptor antagonist (α2A-AR, α2-AR subtype) could also reverse DEX-induced inhibition on Nav1.8current.Under current clamp, DEX could enhance the threshould to evoke action potentials and reduced the firing rate in small DRG neurons.Conclusions: These data indicate that dexmedetomidine reduce Nav1.8 current by the activation of alpha 2 adrenergic receptor and G-protein dependent signaling pathway, whereby resulting in the relief of inflammatory hyperalgesia.