Gabapentin enhances the antinociceptive effects of spinal morphine in the 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 intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 μg and gabapentin at 300 μg produced significant antinociception. Pretreatment with spinal gabapentin at 300 μg shifted the dose-response curve of spinal morphine to the left with a decrease in morphine ED₅₀ value from 1.06 μg to 0.34 μg. The antinociceptive effects produced by the combination of a subantinociceptive dose of morphine and gabapentin were reversed by spinal naloxone at 30 μg but were not reversed by spinal bicuculline at 0.3 μg. Furthermore, the concurrent administration of spinal naloxone at 30 μg with the combination of morphine and gabapentin blocked antinociception, while the concurrent administration of spinal bicuculline at 0.3 μg failed to prevent antinociception. These results indicate that the combination of spinal gabapentin and morphine produces an enhancement of antinociception that appears 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, indicating that tolerance did not develop to gabapentin's ability to enhance morphine antinociception.