Effect of intrathecal oxcarbazepine on rat tail flick test-determined morphine tolerance

Repeated administration of morphine leads to characteristic tolerance. We tested the effects of intrathecal oxcarbazepine (OXC) on spinal morphine tolerance in rats using the tail flick test.

Sprague-Dawley rats received intrathecal injections of 10 microliter saline alone, or 10 microliter of solutions containing 100 microgram OXC, 15 microgram morphine, or OXC + morphine for 7 days. Different groups of rats received OXC on days 1-7, 1-3, or 5-7. The tail-flick assay was used to measure acute and chronic nociception. The nociceptive stimulus consisted of dipping the distal 5 cm of the tail into warm water before and 30 min after drug injection. On day 8, an antinociceptive dose-response curve was plotted, and the 50% effective dose for morphine (given alone) was determined for all groups.

Morphine or OXC both produced acute antinociception; OXC + morphine resulted in a significantly larger response than obtained with morphine alone. Morphine tolerance was produced by intrathecal injection of morphine over 7 days. Co-administration of morphine and OXC completely blocked morphine tolerance, but tolerance developed when OXC injection was stopped, and morphine potency was partially restored by co-administration of OXC in tolerant rats.

The antinociceptive effect of both acute and chronic morphine therapy is increased with intrathecal OXC, and antinociceptive morphine tolerance is attenuated in rats.