Comparison of direct and indirect depressant actions of ketamine on dorsal horn cells in rabbits.

The neurophysiological mechanism for the depressant action of ketamine on nociceptive transmission in the spinal cord was examined in rabbits with an intact spinal cord and those with a transected or cold-blocked spinal cord. Ketamine depressed the nociceptive responses in both intact and transected spinal cord groups dose-dependently. The depressant effects of ketamine were significantly greater and longer in the intact group than in the transected group, particularly with 2 and 5 mg/kg of ketamine. The depressant effects produced by ketamine on activity induced by bradykinin were partially reversed by 1 mg/kg of naloxone. Compared to the reversible cold block of the upper part of the spinal cord, the depressant effects produced by both 2 and 5 mg/kg of ketamine on activity induced by bradykinin in the intact spinal cord were significantly greater, and 10 mg/kg of ketamine depressed the nociceptive responses to similar levels in both states. These results suggest that in small to moderate doses, the indirect depressant action of ketamine from the brain stem is more important than the direct action. On the other hand, at a large dose, the direct depressant action becomes predominant.