Role of NMDA and opioid receptors in neuropathic pain induced by chronic constriction injury of sciatic nerve in rats

The efficacy of opioids in neuropathic pain is still controversial. Earlier studies have suggested that N-methyl-D-aspartate (NMDA) receptor binding can be affected by opioids and vice versa. The present study aims to explore the interactions between NMDA and opioid receptors using various combinations of drugs acting on these receptors. We used an animal model of sciatic nerve ligation to induce neuropathic pain, and a hot-plate test was used to assess pain response. It was observed that NMDA and naloxone increased the pain response. Ketamine reduced the pain response, which was further reduced when ketamine was administered in combination with naloxone, but not with NMDA, thus highlighting the activity of the NMDA receptor system. In addition, morphine was also found to increase latency to hind-paw lick, which was further reduced when given in combination with naloxone. Furthermore, triple drug combinations using ketamine+morphine+naloxone and ketamine+NMDA+naloxone demonstrated some significant interactions at these receptors. Thus, our study establishes that neuropathic pain can probably be overcome using higher doses of opioids, and there exists some intimate relationships between NMDA and opioid systems that lead to pain modulation.