Possible role of NMDA receptors in antinociception induced by rilmenidine in mice in the formalin test.

The aim of the study was to investigate the possible role of MK-801, an NMDA antagonist, in analgesia induced by rilmenidine, an imidazoline (I(1)) agonist, in mice in the formalin test. 25 microl of formalin 2.5% was injected into the dorsal surface of the right hind paw of the mouse. Pain response was scored after formalin injection for a period of 50 min. A weighted average of nociceptive score, ranging from 0 to 3, was calculated. The mean +/-SEM of scores between 0-5 and 15-40 min after formalin injection was presented. The study showed that rilmenidine (1.25, 2.5 and 5 mg/kg, i.p.) produced analgesia dose-dependently (p<0.001) in formalin test. In addition, the results demonstrated that efaroxan (0.1 and 1 mg/kg, i.p.) could reduce the antinociceptive effect of rilmenidine (2.5 mg/kg, i.p.) (p<0.01) in animals, however, yohimbine (0.1 and 0.2 mg/kg, i.p.) could not block the analgesia induced by rilmenidine (2.5 mg/kg, i.p.) (p>0.05). On the other hand, MK-801 (0.05 mg/kg, i.p.) reduced the pain related behaviors in mice (p>0.05). Moreover, our findings demonstrated that MK-801 (0.01 mg/kg, i.p.) could potentiate the analgesic effect of rilmenidine (1.25 mg/kg, i.p.) significantly (p<0.01). The present study suggests that imidazoline (I(1)) receptors play an important role in mediating the antinociception induced by rilmenidine in formalin test. Furthermore, it may be concluded that there is an interaction between NMDA receptors and imidazoline (I(1)) binding sites.