Spinally mediated analgesic interaction between γ-aminobutyric acid B receptor agonist and glutamate receptor antagonists in rats

Background.  Many mechanisms are involved in pain transmission in the spinal cord.  Therefore, combination of drugs acting on different kinds of mechanisms might be useful for analgesia.  We investigated the interaction betweenγ-aminobutyric acid （GABA）B receptor agonist, baclofen, and N-methyl-D-aspartate （NMDA） receptor antagonist, AP-5, orα-amino-3-hydroxy-5-methylisoxazole-4-propionic acid （AMPA） receptor antagonist, YM-872, on analgesic effects in acute thermal and formalin induced pain models of rats. Methods.  Male Sprague-Dawley rats implanted with lumbar intrathecal catheters were given intrathecal baclofen, AP-5, YM872 or combination of baclofen and AP-5 or YM872, then tail flick test or formalin test was performed.  Fifty % effective doses of combinations were obtained and isobolographic analysis was done. Results.  The combination of baclofen and AP-5 or YM872 showed dose dependent increases in tail flick latency and decreases in flinching response in the formalin test.  In the tail flick test, ED50s of the combination of baclofen + AP-5 or YM872 were close to the additive points.  In both phases of the formalin test, ED50s of the combination of baclofen + AP-5 or YM872 were significantly lower than additive points.  Conclusions.  For acute thermal pain, both AP-5 and YM872 had similar additive analgesic effects with baclofen.  For chemical induced acute pain, both AP-5 and YM872 had similar synergistic analgesic effects with baclofen, but for facilitated pain, YM872 had stronger synergistic analgesic effects with baclofen than AP-5.