Peripheral interaction of opioid and NMDA receptors in inflammatory pain in rats.

Both opioid and NMDA receptors have been known to be involved in pain processing in the central nervous system as well as in the periphery. The effect of drugs acting on opioid and NMDA receptors, and their role in modulation of pain response was observed in the formalin model of inflammatory pain in rats. We have demonstrated that morphine has significant antinociceptive effect in the formalin model and this effect was enhanced when given in combination with ketamine. We have also reported modulation of pain response when naloxone or NMDA were co-administered with morphine or ketamine in various combinations. A noteworthy observation in our study is that low dose naloxone when co-administered with ketamine and morphine, or with ketamine and NMDA, caused decrease in the pain response. These observations may suggest that low dose naloxone can cause modulation of opioid and NMDA receptors resulting in antinociceptive effect. Our study thus introduces a new concept of more than two drugs acting on opioid and NMDA receptors to modulate pain response.