MIDAZOLAM ENHANCES THE ANALGESIC PROPERTIES OF DEXMEDETOMIDINE IN THE RAT
Open Access
- Author:
- Boehm, Christine A.
- Graduate Program:
- Laboratory Animal Medicine
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- April 01, 2009
- Committee Members:
- Ronald Paul Wilson, Thesis Advisor/Co-Advisor
Ronald Paul Wilson, Thesis Advisor/Co-Advisor - Keywords:
- antinociception
analgesia
anesthesia
midazolam
dexmedetomidine
tail-flick - Abstract:
- Objective Investigate the antinociceptive properties of intraperitoneal-administered dose combinations of midazolam and dexmedetomidine in the rat. Animals Seventy adult male Sprague Dawley rats (250-300 g) were used in this study. 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 intraperitoneally (i.p.), first alone then in combination (D:M) ranging from 0.03 D:5 M to 0.18 D:30 M mg kg-1. Antinociception was evaluated using the tail-flick test at time 0 (before injection), 15, 30, 45, 60 and 75 minutes. To correlate antinociceptive properties with surgical analgesia, a small pilot study was conducted on four rats anesthetized with 0.06 mg kg-1 D + 10 mg kg-1 M, 0.09 mg kg-1 D + 15 mg kg -1 M, or 0.12 mg kg-1 D + 20 mg kg -1 M administered i.p. Time to loss of righting reflex, presence or absence of pedal reflex, and response to surgical incision were measured. Results Midazolam at all doses administered alone (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 combinations of D and M were significantly greater than D alone (p<0.05). Further analysis of tail-flick latencies at 60 minutes post-administration (presumed steady state) indicated the drug-drug interaction with respect to tail-flick latency was synergistic. Conclusions A dose-related antinociceptive effect was demonstrated for D in the rat, which was enhanced by co-administration of M.