| Co-Investigator(Kenkyū-buntansha) |
HANAOKA Kazuo The University of Tokyo, Anesthesiology, Professor, 医学部附属病院, 教授 (80010403)
TAMAI Hisayoshi The University of Tokyo, Anesthesiology, research associate, 医学部附属病院, 助手 (00272592)
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| Research Abstract |
Splague-Dawley rats were implanted with lumbar intrathecal catheters. Midazolam (GABA_A receptor agonist), AP-5 (NMDA receptor antagonist), YM872 (AMPA receptor antagonist), bupivacaine (local anesthetic), clonidine (α_2 receptor agonist), serotonin (serotonin receptor agonist), and epibatidine (acetyocholine receptor agonist) were examined of their analgesic effects by intrathecai administration using the Tail flick test and Formalin test. All the agents showed dose dependent analgesic effects on both tail flick test and Formalin test and 50% effective doses (ED_<50>) were obtained. The interaction of two agents was examined with the combination of 1/2ED_<50>, 1/4ED_<50>, 1/8ED_<50>, or 1/16ED_<50> of each agent using an isobolographic analysis. Eight rats were used in each dose. Bupivacaine + AP-5, or clonidine, epibatidine + YM872 or clonidine, and midazolam + serotonin, in the Tail flick test, and epibatidine + serotonin, or clonidine in the phase 1 of the Formalin test showed additive effects. Bupivacaine + serotonin, and epibatidine + midazolam in the phase 2 of the Formalin test were antagonistic. No interaction was seen in the phase 2 of the Formalin test with serotonin + midazolam, and epibatidine + serotonin or clonidine. Other combinations in both tests showed significant synergistic analgesic effects.
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