Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats

Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.