Using Cageside Measures to Evaluate Analgesic Efficacy in Mice (Mus musculus) after Surgery

Recent studies have revealed some of the most frequently used analgesics in mice are not effectively treating postoperative pain. Our laboratory sought to compare and assess the validity and reliability of 2 cageside pain assessments that we recently developed for use in mice-nesting consolidation and grooming transfer tests. We then applied these tests to compare the efficacy of commonly used analgesics-buprenorphine (0.1 mg/kg SC every 12 h for 48 h) and carprofen (30 mg/kg in drinking water for 72 h)-alone and in multimodal combination as a refinement for treating postoperative pain in mice. Briefly, C57BL/6 and CD1 male and female mice underwent assessment under conditions of baseline, anesthesia-analgesia, and laparotomy. Results showed that multimodal analgesia displayed the greatest analgesic coverage over the postoperative period, whereas buprenorphine showed slightly less coverage, and carprofen and saline groups displayed signs of pain at most postoperative time points. After anesthesia-analgesia, buprenorphine and multimodal mice lost significant body weight in the absence of a painful stimulus and displayed other significant drug-related changes. Animals treated with carprofen showed few drug-related changes after anesthesia-analgesia but also demonstrated minimal benefit from postsurgical analgesia. Overall, multimodal analgesia was more effective for treating postsurgical pain in mice than the single-analgesic protocols we tested; however, effects on weight loss need to be considered during analgesic selection. Nesting consolidation and grooming transfer tests were valid and highly reliable over time, in inbred and outbred mice, in male and female mice, under different housing conditions. In addition, the nesting consolidation test had excellent reliability between observers. These findings can be used in refining the detection and treatment of postoperative pain in mice.