Interaction of Intrathecally Infused Morphine and Lidocaine in Rats (Part I): Synergistic Antinociceptive Effects

Background: Synergistic antinociception of opioids and local anesthetics has been established in bolus injections but not in long-term use. The somatic and visceral antinociceptive effects of intrathecally infused morphine or lidocaine were characterized, and the nature of the interaction of those agents in rats was evaluated.

Methods: Intrathecal catheters were implanted in rats. Morphine (0.3 to 10 micro sign]g middle dot] kg-1 middle dot] h-1), lidocaine (30-1,000 micro sign]g middle dot] kg-1 middle dot] h-1), a combination of those, or saline was infused intrathecally at a constant rate of 1 micro sign]l/h for 6 days. The tail flick and colorectal distension tests were used to measure the somatic and visceral antinociceptive effects, respectively. Nociceptive tests and motor function tests were repeated on days 1, 2, 3, 4, and 6. Isobolographic analysis was performed on the results of the tail flick test to determine the magnitude of the interaction.

Results: Intrathecally infused morphine produced dose-dependent antinociceptive effects in both the tail flick and the colorectal distension tests. Morphine showed a lower peak percentage maximum possible effect (%MPE) in the colorectal distension test than in the tail flick test. Intrathecal lidocaine also produced dose-dependent antinociceptive effects. Lidocaine infusion at 1,000 micro sign]g middle dot] kg-1 middle dot] h-1 caused motor impairment. Coinfusion of morphine 0.3 micro sign]g middle dot] kg-1 middle dot] h-1 and lidocaine 200 micro sign]g middle dot] kg-1 middle dot] h-1, which had no effects by themselves, significantly increased the percentage maximum possible effects (P < 0.01). Coinfused lidocaine potentiated the duration and the magnitude of morphine antinociception. Isobolographic analysis of the tail flick test on day 1 showed a synergistic interaction between morphine and lidocaine.