Evaluation of analgesic interaction between morphine, dexmedetomidine and maropitant using hot-plate and tail-flick...

To determine if the combinations of morphine, dexmedetomidine and maropitant enhance the analgesic effect and decrease the dose of individual drugs in rats subjected to noxious thermal stimulation with hot-plate and tail-flick tests.

Randomized, blinded, prospective experimental study.

A total of 96 male Sprague-Dawley rats.

The rats were randomly assigned to the following groups: 1) morphine (3 mg kg^-1; Mor); 2) dexmedetomidine (10 μg kg^-1; Dex); 3) maropitant (20 mg kg^-1; Maro); 4) morphine (1.5 mg kg^-1) + dexmedetomidine (5 μg kg^-1; Mor + Dex); 5) dexmedetomidine (5 μg kg^-1) + maropitant (10 mg kg^-1; Dex + Maro); 6) morphine (1.5 mg kg^-1) + maropitant (10 mg kg^-1; Mor + Maro); 7) morphine (1 mg kg^-1) + dexmedetomidine (3.5 μg kg^-1) + maropitant (6.5 mg kg^-1; Mor + Dex + Maro); and 8) normal saline (0.5 mL; saline), all injected intravenously. The tail-flick and hot-plate tests were performed before and 5, 15, 30, 45, 60, 90 and 120 minutes after the injection of the drugs. These variables were analysed with the effect-time area under the curve (AUC) analysis and a mixed linear model.

Data were analysed in 94 rats. The rank order of the total analgesic effects of the treatment groups shown by AUC analysis was found to be Mor > Maro + Mor > Dex + Mor > Dex > Maro > Dex + Maro + Mor > Dex + Maro > saline for the hot-plate test, and Maro + Mor > Mor > Dex + Mor > Dex + Maro + Mor > Maro > Dex > Dex + Maro > saline for the tail-flick test. The mixed model analysis showed a significant difference between latencies of the group morphine + maropitant versus all other treatment groups in the tail-flick test (p < 0.0001) and morphine versus saline in the hot-plate test (p < 0.05).

Morphine and maropitant appeared to show a supra-additive effect for analgesia in the tail-flick test. Clinical trials should be conducted to establish its use in treating pain.