ANTINOCICEPTIVE EFFECT INDUCED BY THE COMBINED ADMINISTRATION OF SPINAL MORPHINE AND SYSTEMIC BUPRENORPHINE

We evaluated the antinociceptive effect of combined spinal administrat ion of morphine and systemic administration of buprenorphine. Experime nts 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 impl anted in the subarachnoid space. Interaction of drugs was analyzed usi ng a dose addition model. Both IT (1-5 mu g) morphine and IP (50-500 m u g/kg) buprenorphine increased the latencies of nociceptive responses in a dose-dependent manner. IT morphine (4 mu g) and IP buprenorphine (100 mu g/kg) produced 62.9 +/- 6.3 and 48.8 +/- 6.6 percent of the m aximal possible effect (%MPE), respectively. The combined administrati on of 2 mu g of IT morphine and 50 mu g/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 co ncurrent administration of spinal morphine and systemic buprenorphine produces an antinociceptive effect that is greater than what could hav e been predicted from individual dose-response curves. This mode of in teraction allows maintenance at a significant level of analgesia with reduced doses of opioids, which minimizes the incidence of undesirable side effects.