Effects of orally administered metamizole, tramadol, and buprenorphine on postsurgical recovery in mice

Introduction: The implantation of telemetric devices is widely used in preclinical research to enable real-time monitoring of physiological parameters while minimizing handling-related distress and artifacts. The intraperitoneal implantation remains highly invasive and requires analgesia to ensure animal welfare and data integrity. Due to limited evidence about long-term effects, particularly in the case of voluntary oral administration, choosing adequate analgesics remains challenging. Objectives: This study aimed to evaluate and compare the short- and long-term effects, tolerability, and the supportive value of orally administered metamizole, tramadol, and buprenorphine in mice before and after intraperitoneal transmitter implantation. Methods: A comprehensive, multiparametric approach combining physiological, behavioral, telemetry-derived, and clinical chemistry data was applied to assess treatment-dependent distress and physiological changes in BALB/c mice of both sexes. Results: In healthy mice, all treatments initially led to reductions in body weight and water intake, with the mildest changes under buprenorphine treatment. Postoperatively, metamizole was associated with the most pronounced and prolonged impairments in body weight, water intake, and activity. The RELSA scores confirmed significantly higher distress under metamizole treatment during early recovery. Buprenorphine and tramadol promoted faster normalization of well-being indicators. After full recovery, buprenorphine treatment was linked to higher water intake and body temperature, while metamizole caused persistently low water intake. In buprenorphine- and tramadol-treated mice, changes in blood counts were observed, and mild hyperthermia was detected under buprenorphine treatment. A limitation of the study is the absence of a control group, as analgesic treatment is ethically and legally required. Conclusion: Buprenorphine and tramadol support rapid and sustained recovery after transmitter implantation, while metamizole is associated with prolonged postoperative burden and changes in liver enzymes. Treatment with buprenorphine or tramadol showed favorable recovery profiles with mild long-term physiological effects. These findings contribute to evidence-based refinement of analgesic strategies, improving both animal welfare and experimental validity.