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

Objectives: 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. Methods: 25μl 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 50min. A weighted average of nociceptive score, ranging from 0 to 3, was calculated. The mean ±SEM of scores between 0–5 and 15–40min after formalin injection was presented. Results: The study showed that rilmenidine (1.25, 2.5 and 5mg/kg, i.p.) produced analgesia dose‐dependently ( p <0.001) in formalin test. In addition, the results demonstrated that efaroxan (0.1 and 1mg/kg, i.p.) could reduce the antinociceptive effect of rilmenidine (2.5mg/kg, i.p.) ( p <0.01) in animals, however, yohimbine (0.1 and 0.2mg/kg, i.p.) could not block the analgesia induced by rilmenidine (2.5mg/kg, i.p.) ( p >0.05). On the other hand, MK‐801 (0.05mg/kg, i.p.) reduced the pain related behaviors in mice ( p >0.05). Moreover, our findings demonstrated that MK‐801 (0.01mg/kg, i.p.) could potentiate the analgesic effect of rilmenidine (1.25mg/kg, i.p.) significantly ( p <0.01). Conclusions: 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.