SPINALLY MEDIATED ANALGESIC INTERACTION BETWEEN MORPHINE AND MIDAZOLAM, CLONIDINE, SEROTONIN, BUPIVACAINE, EPIBATIDINE, NEOSTIGMINE, CARBACHOL, OR BACLOFEN IN RATS: WHICH IS THE MOST EFFECTIVE COMBINATION?
Tomoki Nishiyama MD, PhD*
ABSTRACT
Background: The purpose was to find out the best combination between intrathecal morphine and midazolam, clonidine, serotonin, bupivacaine, epibatidine, neostigmine, carbachol, or baclofen in analgesic effects when intrathecally administered. Methods: Male Sprague-Dawley rats implanted with lumbar intrathecal catheters were given intrathecal combination of morphine and midazolam, clonidine, serotonin, bupivacaine, epibatidine, neostigmine, carbachol, or baclofen, then tail flick test or formalin test was performed. Isobolographic analysis was done using 50 % effective doses (ED50s), and total fractional dose values were calculated. Results: The ED50s of the combination were significantly lower than those of each drug alone in all drugs tested in both tail flick test and formalin test. The ED50 of morphine in the combination was the lowest with baclofen in the tail flick test and with neostigmine in both phases of the formalin test. Total dose fractional value was the lowest with baclofen (0.03) in the tail flick test and with neostigmine (0.006 in phase 1 and 0.00028 in phase 2) in the formalin test. Conclusions: Baclofen for acute thermal pain and neostigmine for inflammatory pain are the best to combine with morphine when intrathecally administered in all tested drugs.
Keywords: Spinal analgesia, morphine, interaction, rat.
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