Jirkof, P., Arras, M., Cesarovic, N. 2018. Tramadol:Paracetamol in drinking water for treatment of post-surgical pain in laboratory mice. Applied Animal Behaviour Science 198, 95-100.

In the search for stress-free analgesia administration for laboratory mice suffering pain, oral delivery of Tramadol:Paracetamol (T:P) shows great promise. Here, we monitored the analgesic efficacy and side effects of a T:P combination administered solely in the drinking water of female C57BL/6J mice after moderate-impact surgery (sham embryo transfer), using clinical and behavioral pain and recovery parameters. Animals underwent anesthesia and surgery with T:P treatment (OP+T:P), received no pain relief after surgery (OP), underwent anesthesia only with T:P treatment (An+T:P) or T:P treatment only (T:P). Indicators of pain and constraint were assessed at several time points during 24h after surgery. T:P-containing drinking water was consumed readily in amounts to assure sufficient drug levels. No obvious detrimental side effects of analgesia were observed. General condition of animals differed only slightly and non-significantly between treatment groups, with comparable post-procedural weight loss, water and food intake as well as home cage activity. Mean nest scores differed significantly between T:P and both surgery groups (p=0.002, p<0.0001) but revealed no significant difference between OP and OP+T:P groups. Nevertheless, pain scores showed significant differences between the treatment groups at 1, 3 and 6h after surgery (p=0.001, p=0.014, p=0.003). OP animals scored highest, while scores of OP+T:P animals were comparable or lower than scores of the AN+T:P group. Same was true for burrowing latency that was significantly increased in OP animals compared to An+T:P and OP+T:P (p=0.032, p=0.019), but comparable between An+T:P and OP+T:P. These results hint on a clear post-surgical pain effect after surgery that could be significantly reduced with T:P treatment towards a level of the control group receiving anesthesia and T:P only. In conclusion, we assume that orally administered T:P offers pain relief with no obvious side effects after mild-to-moderate impact surgery in female C57BL/6J mice.