Background: 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.
Methods: 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.
Results: 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.
Conclusions: The antinociceptive effect of both acute and chronic morphine therapy is increased with intrathecal OXC, and antinociceptive morphine tolerance is attenuated in rats.
Keywords: Intrathecal; Morphine; Oxcarbazepine; Tail flick test; Tolerance.