α₂ adrenoceptors are widely distributed in the central nervous system and involved in various physiological functions such as analgesia, hypnosis, amnesia and circulation. α₂ agonists generally used as sedative agents, are also known to have analgesic properties. Previous in vitro studies have shown detailed cellular actions of α₂ agonists by using electrophysiological analyses. In the locus coeruleus (LC) of the brain stem, α₂ agonists are thought to inhibit LC neuronal activity to exert their sedative actions. In the spinal cord, dexmedetomidine (DEX), a highly selective α₂ agonist, directly hyperpolarized substantia gelatinosa (SG, lamina II of the spinal cord) neurons by activating α_2A and α_2C adrenoceptors. Little is known, however, how systemically administered α₂ agonists modulates noxious transmission at the synaptic level in vivo. We made in vivo whole-cell patch-clamp record­ings from SG neurons in adult anesthetized rats and examined analgesic action of systemically administered DEX. Contrary to our expection, intravenous administration of DEX at doses of sedative range did not induced any hyperpolarization in all SG neurons tested. Interestingly, DEX at doses below sedative range dramatically enhanced spontaneous inhibito­ry postsynaptic currents (IPSCs) in most of SG neurons tested. This facilitatory action of DEX was completely disappeared in spinalized rats, and spinal application of prazosin, an α₁ antagonist, inhibited the facilitation of spinal IPSCs by DEX. These results suggest that systemically administered DEX at doses below sedative range paradoxically enhances descending noradrener­gic inhibitory pathway and results in facilitation of inhibitory synaptic transmission in the spinal dorsal horn. Our findings provide a new insight into the usefulness of α₂ agonists for therapeutic intervention against acute and chronic pain.