Abstract
Background: Reliable analgesia is essential to ensure animal welfare and experimental validity in preclinical disease models. However, evidence on the efficacy and side effects of analgesics remains limited. This study investigated the effects of three commonly used analgesics on animal well-being in a murine model of cholestasis. Methods: Thirty male C57BL/6J mice underwent transmitter implantation followed by bile duct ligation (BDL) and received continuous metamizole (3 g/L), tramadol (1 g/L), or carprofen (0.15 g/L) via drinking water before and after surgery. Welfare was evaluated using multiple parameters, including body weight, a distress score, drinking volume, burrowing and nesting behavior, mouse grimace scale (MGS), and telemetric data (heart rate, heart rate variability: SDNN and RMSSD, core body temperature, and locomotion). Additionally, liver and gastrointestinal tissues were analyzed histologically for necrosis and immune cell infiltration. Results: Even prior to surgery, analgesic-specific reductions in body weight, drinking behavior, and burrowing and nesting activity were observed. After transmitter implantation, metamizole treatment led to significantly reduced body weight, drinking volume, and locomotion compared to the other two analgesics. Following BDL, all treatment groups exhibited pronounced distress, weight loss, and reduced activity. Tramadol treatment resulted in slightly improved MGS and SDNN values, indicating minor benefits without sustained welfare restoration. In contrast, carprofen treatment was associated with reduced survival and inflammatory alterations in the forestomach. Conclusions: None of the tested analgesic regimens fully restored animal welfare after BDL. However, tramadol provided modest advantages, suggesting it may represent the most suitable option among the tested analgesics for the BDL model.