Oxcarbazepine is an
anticonvulsant drug that has been explored as a novel therapeutic agent to treat
neuropathic pain in humans. It produces antinociception in several preclinical models of
pain, and these actions are blocked by
methylxanthine adenosine receptor antagonists which implicates
adenosine it its actions. In this study, the antinociceptive effect of
oxcarbazepine, and the ability of
caffeine to reverse its actions, were examined using the
formalin test (2%) in wild-type mice and in mice lacking
adenosine A(1) receptors by way of further exploring the involvement of
adenosine in its actions.
Oxcarbazepine produced dose-related suppression of
formalin-evoked flinching responses in wild-type mice following both systemic and intraplantar administration, and this action was reversed by systemic and intraplantar administration of
caffeine, respectively. The ability of
oxcarbazepine to inhibit flinching after systemic and intraplantar administration was unaltered in homozygous (-/-) and heterozygous (+/-)
adenosine A(1) receptor knockout mice. However,
caffeine no longer reversed this antinociception. Our results indicate that, while
adenosine A(1) receptors are not required for
oxcarbazepine to produce antinociception in knockout mice, such receptors are essential in order to see
caffeine reversal of this antinociceptive effect.