When intrathecally or epidurally administered, α2-adrenoceptor agonists produce potent antinociception by affecting the activity of primary afferent fibres and spinal cord neurons. Recent reports have indicated that in dorsal root ganglion neurons, tetrodotoxin-resistant Na+ channels play important roles in the conduction of nociceptive sensation. We therefore investigated the effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ currents.

Using the whole-cell patch-clamp technique, we recorded tetrodotoxin-resistant Na+ currents from rat dorsal root ganglion neurons.

Both clonidine and dexmedetomidine reduced the peak amplitude of the tetrodotoxin-resistant Na+ current concentration- and use-dependently. The concentration required for a half-maximal effect was significantly lower for dexmedetomidine (58.0 ± 10.2 μmol) than for clonidine (257.2 ± 30.9 μmol) at holding potential −70 mV. The current inhibitions induced by these agonists were not prevented by 1 μmol yohimbine, an α2-adrenoceptor antagonist. Both clonidine and dexmedetomidine shifted the inactivation curve for the tetrodotoxin-resistant Na+ current in the hyperpolarizing direction. The combinations clonidine with lidocaine and dexmedetomidine with lidocaine produced an additive blockade-type interaction on the tetrodotoxin-resistant Na+ current.

The results suggest that a direct inhibition of tetrodotoxin-resistant Na+ channels may contribute to the antinociceptive effects of clonidine and dexmedetomidine when used as additives to regional anaesthesia.