Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord

Dexmedetomidine is a highly specific, potent and selective α(2)-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n= 84), bath-applied dexmedetomidine induced outward currents at −70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 μm). The outward currents induced by dexmedetomidine were suppressed by the α(2)-adrenoceptor antagonist yohimbine, but not by prazosin, an α(1)-, α(2B)- and α(2C)-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the α(2C)-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the α(2A)-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the α(2A)-adrenoceptor agonist oxymetazoline. Plots of the current–voltage relationship revealed a reversal potential at around −86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-β-S [guanosine-5′-O-(2-thiodiphosphate)] or Cs(+) to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K(+) channels through α(2A)- and α(2C)-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.