Midazolam enhances the analgesic properties of dexmedetomidine in the rat

Objective To investigate the analgesic properties of different dose combinations of midazolam and dexmedetomidine administered intraperitoneally (IP) in the rat. Study design Prospective experimental trial. Animals Seventy adult male Sprague Dawley rats weighing 250-300 g. Methods Dexmedetomidine (D) 0.03, 0.06, 0.09, 0.12, 0.15, 0.18, 0.21 mg kg-1 and midazolam (M) 5, 10, 25, 50 mg kg-1 were administered IP, alone then in combinations ranging from 0.03 D:5 M to 0.18 D:30 M mg kg-1. Analgesia was evaluated using the tail-flick test at time 0 (before injection), 15, 30, 45, 60 and 75 minutes. Results Midazolam at all doses administered (5-50 mg kg-1) did not significantly change tail-flick latencies from baseline values whereas D showed clear dose-dependent increases in tail-flick latency for doses administered in the range of 0.03-0.18 mg kg-1. Tail-flick latencies in rats administered D + M combinations were significantly greater than D alone (p < 0.05). Conclusions A dose-related analgesic effect was demonstrated for D in the rat, which was enhanced by co-administration of M. Clinical relevance The combination of D + M administered IP to rats at doses of 0.12:20 and 0.09:15 mg kg-1 was shown to be a good combination to provide sedation/analgesia with a duration of action greater than 60 minutes. The onset of sedation was rapid (1-3 minutes), and onset of profound analgesia was reached within 5-10 minutes.