Peripheral Antinociceptive Action of Morphine and the Synergistic Interaction with Lamotrigine

Background: Lamotrigine inhibits glutamate release through the preferential blockade of voltage-dependent Na channels. In contrast, morphine reduces release of excitatory amino acids through the activation of opioid receptors and also inhibits tetrodotoxin-resistant Na channels on peripheral afferent neurons. The current study was designed to investigate the antinociceptive effects of locally administered morphine and lamotrigine. The interaction between morphine and lamotrigine at the periphery was also examined. Methods: Morphine, lamotrigine, or a combination of morphine and lamotrigine was administered locally to female Wistar rats, and the antinociceptive effect was determined in the formalin test. Isobolographic analyses were used to define the nature of the functional interactions between morphine and lamotrigine. Results: Peripheral administration of either morphine or lamotrigine produced a dose-related antinociceptive effect. Isobolographic analyses revealed that peripheral morphine and lamotrigine interacted synergistically in the formalin test. Conclusions: The study shows a functional interaction between lamotrigine and morphine at the peripheral level. LAMOTRIGINE is an anticonvulsant drug suggested to be an effective analgesic in the treatment of pain in rats. Either oral or intrathecal administration of lamotrigine produces a dose-dependent antinociception in rat experimental models of acute and chronic pain. 1,2 Studies on neuropathic pain showed that this drug could reverse cold allodynia, but not tactile allodynia, and it also reduced the development of neuropathic pain. 3 Clinical studies have also shown that lamotrigine is able to reduce neuropathic pain after oral administration. 4– 7 However, other studies have failed to find an analgesic effect in neuropathic pain. 8 The antinociceptive effect of lamotrigine has been attributed to the blockade of voltagedependent Na channels with the inhibition of glutamate release. 9