ANALGESIC INTERACTION BETWEEN INTRATHECALLY ADMINISTERED BUPIVACAINE AND EPIBATIDINE IN RATS
*Tomoki Nishiyama MD, PhD
ABSTRACT
Background: We investigated the interaction between intrathecally administered bupivacaine and epibatidine, a nicotinic acetylcholine receptor agonist, on analgesic effects in acute thermal and formalin induced pain models of rats. Methods: Male Sprague-Dawley rats implanted with lumbar intrathecal catheters were given intrathecal combination of 1/2, 1/4, 1/8, and 1/16 50% effective doses (ED50s) of bupivacaine and epibatidine, then tail flick test or formalin test was performed. Isobolographic analysis was done using ED50s, and total fractional dose values were calculated. Behavioral side effects were checked. Results: In the tail flick test, ED50 of the combination was not obtained. Dose dependent decreases of number of flinch response were observed in the formalin test. The ED50s of both phase 1 and 2 of the formalin test were significantly lower than the theoretical additive values. Side effects were not observed in this study. Conclusions: Intrathecal bupivacaine and epibatidine had antagonistic effects on thermal induced acute pain, but synergistically analgesic for inflammatory induced acute and chronic pain.
Keywords: Analgesia, nicotinic acetylcholine receptor, epibatidine, bupivacaine, spinal cord.
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