Intrathecal lamotrigine blocks and reverses antinociceptive morphine tolerance in rats

Chronic administration of morphine leads to the development of tolerance. We investigated the effects of intrathecal lamotrigine on the spinal morphine tolerance in rats that are undergoing tail flick tests.

Sprague-Dawley rats were given intrathecal injections of saline 10 microl, lamotrigine 300 microg, morphine 15 microg or lamotrigine plus morphine combinations for 7 days (lamotrigine was given for days 1-7, days 1-3 or days 5-7). The acute and chronic nociceptive sensitivities were assessed using a tail flick test in which the distal 5 cm of the tail was dipped into warm water before and 30 minutes after the drug injection. With successive injections of morphine on day 8, a cumulative antinociceptive dose-response curve was constructed and the 50% effective dose (ED50) was calculated for each study group.

The coinjection group of lamotrigine with morphine blocked the development of tolerance, as was shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group. Coinjection of lamotrigine blocked the development of morphine tolerance, as shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group.

This study suggests that lamotrigine augments the antinociceptive action of both acute and chronic morphine therapy, and it also attenuates the antinociceptive morphine tolerance in rats.