We evaluated the antinociceptive effect of combined spinal administration of morphine and systemic administration of buprenorphine. Experiments were performed on male Wistar rats. Nociception was measured using the tail immersion test. Buprenorphine was injected intraperitoneally (IP) and morphine was injected intrathecally (IT) via a catheter implanted in the subarachnoid space. Interaction of drugs was analyzed using a dose addition model. Both IT (1-5 microg) morphine and IP (50-500 microg/kg) buprenorphine increased the latencies of nociceptive responses in a dose-dependent manner. IT morphine (4 microg) and IP buprenorphine (100 microg/kg) produced 62.9+/-6.3 and 48.8+/-6.6 percent of the maximal possible effect (%MPE), respectively. The combined administration of 2 microg of IT morphine and 50 microg/kg IP buprenorphine produced a %MPE of 97.1+/-3.4. The analysis of drug interaction revealed that IT morphine interacted with IP buprenorphine in a supraadditive manner while producing a potent antinociceptive effect.
Implications: The concurrent administration of spinal morphine and systemic buprenorphine produces an antinociceptive effect that is greater than what could have been predicted from individual dose-response curves. This mode of interaction allows maintenance at a significant level of analgesia with reduced doses of opioids, which minimizes the incidence of undesirable side effects.