European Journal of Biomedical and Pharmaceutical Sciences

SPINALLY MEDIATED ANALGESIC INTERACTION BETWEEN GLUTAMATE RECEPTOR ANTAGONISTS AND BUPIVACAINE, MORPHINE, EPIBATIDINE, OR SEROTONIN 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 N-methyl-D-aspartate （NMDA）receptor antagonist (AP-5), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid （AMPA） receptor antagonist (YM-872) and bupivacaine, morphine, serotonin, or nicotinic acetylcholine receptor agonist (epibatidine) in analgesic effects. Methods; Male Sprague-Dawley rats implanted with lumbar intrathecal catheters were given intrathecal combination of AP-5 or YM872 and bupivacaine, morphine, 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: In the tail flick test, AP-5 and bupivacaine, and YM 872 and epibatidine showed additive effects, and in the phase 2 of the formalin test, AP-5 and epibatidine had antagonistic effects. Other combinations in both tail flick test and formalin test showed synergistic effects. Morphine showed smallest total fractional dose value in both tail flick test and formalin test. Conclusions: When combined with intrathecal AP-5 or YM872, intrathecal morphine showed most potent analgesia in the agents tested for acute thermal and inflammatory acute and facilitated pain. Intrathecal epibatidine with AP-5 enhanced inflammation induced facilitated pain.

Keywords: NMDA receptor, AMPA receptor, Local anesthetic, ?-opioid receptor, Nicotinic acetylcholine receptor, Serotonin.