A Retrospective Report of Carprofen Administration as Post-Operative Analgesia Reveals Negative Effects of Recommended Doses

Abstract

Effective pain management in laboratory animals is crucial for both animal welfare and the reliability of scientific research. We retrospectively examined the effects of carprofen as post-operative analgesia in Sprague Dawley rats following stereotactic surgery. Our data indicate that administering carprofen twice daily (5 mg/kg), as currently recommended by Die Gesellschaft für Versuchstierkunde/Society for Laboratory Animal Science (GV-SOLAS), led to adverse effects such as reduced food and water intake, disrupted fecal excretion, and abdominal bloating consistent with peritonitis. Continued administration exacerbated these symptoms, with post-mortem findings of intestinal obstructions and ulcers. However, when the frequency was reduced to once daily, such adverse symptoms were not observed. These results are based on incidental data collected from various neuroscientific experiments, resulting in small and uneven sample groups across various experimental cohorts. The inherent imbalances in these groups present challenges for statistical interpretation. While the findings suggest that less frequent carprofen use may reduce adverse effects, the surgical interventions and concurrent use of other drugs in these experiments likely exacerbated these outcomes. Further investigation into the interactions between carprofen, surgical stress, and other perioperative factors is needed to refine analgesia protocols in laboratory animals. Despite these limitations, these observations contribute to understanding analgesia protocols and may assist in improving animal welfare practices.

Keywords: analgesia; animal welfare; laboratory animals; multimodal drug administration; refinement; stereotactic surgery.

Figure 1

Original analgesia protocol vs. refined analgesia protocol. Schematic comparing the original analgesia protocol with the current refined model for our experimental purposes. The black arrows represent default carprofen administration per the approved timeline; the grey arrows indicate observation-based administration, including emergency treatments for unexpected symptom presentation (see post-operative care section). Both protocols include a minimum of a 3-day post-surgical observation, including a recording of the daily weight, as well as documentation of animal monitoring, including any symptoms of pain or discomfort, along with wet food supplementation; in both protocols, any possible extension of post-OP care is based on individual observations. The left column describes the original analgesia treatment, with carprofen automatically administered twice daily (spread across visits in the morning and evening) for 3 days post-OP. The right column displays the refined analgesia treatment, where carprofen is applied once daily for 2 days. Additional applications of carprofen can be further applied as needed, provided there is a minimum of 12 h between doses, and no gastrointestinal (GI) issues are found. In case of GI issues, carprofen is replaced with metamizole. The refined protocol tailors treatment to precise observations and considers carprofen’s impact on the gastric system. The original post-OP protocol resulted in high incidence of peritonitis-indicative symptoms, while refined post-OP protocols resulted in zero incidence of such symptom presentation.

Figure 2

Rat health status. (a) Frequency of health status, treatment protocol, and sex. Blue shades: low frequency carprofen treatment; red/orange shades: high frequency carprofen treatment; brighter shades: female rats; medium shades: male rats; solid black outline: symptomatic (symp.) rats; no outline: healthy rats. The number of animals in each group is labelled in white text. (b) Box plot visualizing the distribution (median value: center bar; interquartile range: shaded box; minimum and maximum values: whiskers) of body weights of all symptomatic rats vs. all healthy rats (left) and symptomatic rats vs. healthy rats within the high frequency carprofen group. (c) Stacked bar plot visualizing the number of symptomatic and healthy animals per surgery type. The number of each surgery type and health outcome used to analyze the effect of surgery on health status is labelled in white on each bar. The bars are overlaid with a line pattern indicating where the animals underwent high frequency carprofen treatment.