Anesthesia & Analgesia, Vol 87, 583-586, Copyright © 1998 by International Anesthesia Research Society
Antinociceptive effect induced by the combined administration of spinal morphine and systemic buprenorphine
D Niv, A Nemirovsky, J Metzner, V Rudick, I Jurna and G Urca
Department of Anesthesiology, Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University.
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.