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 microg x kg(-1) x h(-1)), lidocaine (30-1,000 microg x kg(-1) x h(-1)), a combination of those, or saline was infused intrathecally at a constant rate of 1 microl/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 microg x kg(-1) x h(-1) caused motor impairment. Coinfusion of morphine 0.3 microg x kg(-1) x h(-1) and lidocaine 200 microg x kg(-1) x 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.


CONCLUSIONS
Morphine and lidocaine intrathecally coadministered synergistically potentiated the antinociceptive effects of each other. That coinfusion dramatically potentiated visceral antinociception, whereas the infusion of morphine alone showed little visceral antinociception.
Saito
Y
Y
Department of Anesthesiology, Shimade Medical University, Japan. ysaito@shimane-med.ac.jp
Kaneko
M
M
Kirihara
Y
Y
Sakura
S
S
Kosaka
Y
Y
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012007:Rectum / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000502:physiology
D000700:Analgesics; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D009020:Morphine; D008012:Lidocaine