COMPARISON OF ANALGESIC EFFECTS BETWEEN SEROTONIN AND EPIBATIDINE WHEN COMBINED WITH CLONIDINE BY INTRATHECAL ADMINISTRATION IN RAT MODELS
*Tomoki Nishiyama MD, PhD
ABSTRACT
Background: The present study was performed to compare analgesic effects of the combination of intrathecal clonidine and serotonin with that of clonidine and epibatidine to know whether serotonin or epibatidine is better to combine with clonidine in intrathecal analgesia. Methods: Male Sprague-Dawley rats implanted with lumbar intrathecal catheters were given intrathecal combination of clonidine with serotonin or epibatidine, then tail flick test or formalin test was performed. Isobolographic analysis was done using 50 % effective doses, and total fractional dose values were calculated. Results: Tail flick latency increased with clonidine + serotonin compared to the control. Higher doses of clonidine + epibatidine increased tail flick latency, while lower doses decreased it. Clonidine + serotonin showed synergistic effect in the tail flick test. Clonidine + epibatidine showed additive effect in the tail flick test. The number of flinches in the formalin test decreased with clonidine + serotonin, and clonidine + epibatidine, but not dose dependent. Synergistic effects were observed in both phases of the formalin test with clonidine + serotonin. Additive effect in the phase 1 and antagonistic effect in the phase 2 were observed in the formalin test with clonidine + epibatidine. Conclusions: For acute thermal and acute and chronic inflammatory pain, clonidine + serotonin might be better than clonidine + epibatidine when intrathecally administered.
Keywords: Nicotinic acetylcholine receptor, epibatidine, serotonin, ?2-adrenoceptor, clonidine, intrathecal, analgesia.
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