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

Objective 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. Study design Randomized, blinded, prospective experimental study. Animals A total of 96 male Sprague-Dawley rats. Methods The rats were randomly assigned to the following groups: 1) morphine (3 mg kg(-1); Mor); 2) dexmedetomidine (10 mg kg(-1); Dex); 3) maropitant (20 mg kg(-1); Maro); 4) morphine (1.5 mg kg(-1)) thorn dexmedetomidine (5 mg kg(-1); Mor thorn Dex); 5) dexmedetomidine (5 mg kg(-1)) thorn maropitant (10 mg kg(-1); Dex thorn Maro); 6) morphine (1.5 mg kg(-1)) thorn maropitant (10 mg kg(-1); Mor thorn Maro); 7) morphine (1 mg kg(-1)) thorn dexmedetomidine (3.5 mg kg(-1)) thorn maropitant (6.5 mg kg(-1); Mor thorn Dex thorn 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 effectetime area under the curve (AUC) analysis and a mixed linear model. Results 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 thorn Mor > Dex thorn Mor > Dex > Maro > Dex thorn Maro thorn Mor > Dex thorn Maro > saline for the hot-plate test, and Maro thorn Mor > Mor > Dex thorn Mor > Dex thorn Maro thorn Mor > Maro > Dex > Dex thorn Maro > saline for the tail-flick test. The mixed model analysis showed a significant difference between latencies of the group morphine thorn 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). Conclusions and clinical relevance 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.