Midazolam enhances the analgesic properties of dexmedetomidine in the rat

Abstract

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.

Figure 1

Effects of IP administration of M (mg kg⁻¹) on tail-flick latency in rats. Each bar represents the mean ± SD of group (n = 5) tail-flick latency expressed as percent maximum possible effect (MPE%).

Figure 2

Effects of IP administration of D (mg kg⁻¹) on tail-flick latency in rats. Each bar represents the mean ± SD of group (n = 5) tail-flick latency expressed as percent maximum possible effect (MPE%). * and #, significantly different (p < 0.05) from corresponding higher doses of drug at specified time points.

Figure 3

Effects of IP co-administration of D (mg kg⁻¹) and M (mg kg⁻¹) on tail-flick latency in rats. Each bar represents the mean ± SD of group (n = 5) tail-flick latency expressed as percent maximum possible effect (MPE%). * and #, significantly different (p < 0.05)from corresponding higher doses of drug at specified time points.

Figure 4

Dose–response (tail-flick latency) for D versus D + M at steady state (60 minutes post-injection). All doses expressed as mg kg⁻¹. *Significantly different (p < 0.05) from the same dose of dexmedetomidine alone.