The NMDA receptor is central in the generation and maintenance of chronic pain. This receptor has several sites of modulation. One is the glutamate recognition site that can be blocked by (±)-3-(2-carboxypiperazin-yl)propyl-1-phosphoric acid or (±)-CPP. We investigated whether the effect of glial inhibition produced by propentophylline (PPF) can be enhanced when combined with (±)-CPP. We used Sprague-Dawley rats with experimental monoarthritis, administering intrathecally the ED30 for both drugs (3.97 μg of (±)-CPP and 1.42 μg of PPF), since this combination produces an antinociceptive supra-additive effect when used in mechanical nociception (Randall-Selitto test). The combination of (±)-PPF and CPP produced an antinociceptive effect which was greater than that each drug alone as tested by both the C reflex and windup. We conclude that the antinociceptive effect of the combination of (±)-PPF and CPP possibly generates a supra additive interaction type in monoarthritic rats.