GABAPENTIN ENHANCES THE ANTINOCICEPTIVE EFFECTS OF SPINAL MORPHINE INTHE RAT TAIL-FLICK TEST

The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathe cal coadministration of a subantinociceptive dose of morphine at 0.2 m u g and gabapentin at 300 mu g produced significant antinociception. P retreatment with spinal gabapentin at 300 mu g shifted the dose-respon se curve of spinal morphine to the left with a decrease in morphine ED 50 value from 1.06 mu g to 0.34 mu g. The antinociceptive effects prod uced by the combination of a subantinociceptive dose of morphine and g abapentin were reversed by spinal naloxone at 30 mu g but were not rev ersed by spinal bicuculline at 0.3 mu g. Furthermore, the concurrent a dministration of spinal naloxone at 30 mu g with the combination of mo rphine and gabapentin blocked antinociception, while the concurrent ad ministration of spinal bicuculline at 0.3 mu g failed to prevent antin ociception. These results indicate that the combination of spinal gaba pentin and morphine produces an enhancement of antinociception that ap pears to involve the spinal mu opioid receptors. Furthermore, repeated administration of gabapentin for 3 days did not affect the enhancing effect of gabapentin on the antinociceptive effect of morphine, indica ting that tolerance did not develop to gabapentin's ability to enhance morphine antinociception. (C) 1997 international Association for the Study of Pain. Published by Elsevier Science B.V.