Abstract
INTERACTION BETWEEN MIDAZOLAM AND BACLOFEN IN SPINALLY MEDIATED ANALGESIA IN RATS

Tomoki Nishiyama MD, PhD*

ABSTRACT

Background: We investigated the interaction betweenγ-aminobutyric acid(GABA)A receptor agonist, midazolam and GABAB receptor agonist, baclofen 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 midazolam and baclofen, then tail flick test or formalin test was performed. Isobolographic analysis was done using ED50s, and total fractional dose values were calculated. Results: Intrathecal midazolam and baclofen showed dose dependent increase of tail flick latency and decrease of flinch response in the formalin test. The ED50s of midazolam and baclofen in combination were significantly lower than each agent alone and additive values. Total fractional dose values were 0.37 (0.17 – 0.81, 95%CI), 0.39 (0.12 – 0.95), and 0.13 (0.03 – 0.75) in the tail flick test, phase 1, and phase 2 of the formalin test, respectively. Behavioral side effects observed in each agent were not seen in the combination treatment. Conclusions: Intrathecally administered combination of midazolam and baclofen had synergistic analgesia in thermal induced acute pain and formalin induced acute and facilitated pain without any behavioral side effects.

Keywords: Analgesia, GABAA receptor, GABAB receptor, Spinal cord.


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