Adverse effects of incorporating ketoprofen into established rodent studies

The use of analgesics to prevent or treat postprocedural pain in rodents is increasingly encouraged by the laboratory animal community and federal funding agencies. However, the effects of analgesics on experimental outcomes are not well-documented. In this study, we incorporated ketoprof en into a well-established experimental protocol. Of the 44 Sprague-Dawley (SD) rats obtained from vendor A that were given either ketoprof en (10 mg/kg SC) or saline and underwent ovariectomy, 19 that received ketoprof en died or were euthanized due to clinical illness within 3 to 7 d after surgery. Necropsy revealed gastrointestinal ulceration consistent with toxicity from nonsteroidal antiinflammatory drug. In an attempt to identify factors responsible for this unanticipated outcome, SD rats from vendors A and B were subjected to the same protocol, but no clinical signs or pathologic lesions were observed in any of these rats, regardless of source. A third experiment with rats obtained from vendor A and housed in barriers 1 and 2 was done to clarify the conflicting results and to determine whether response to ketoprofen differed at the barrier level. Three of the 6 rats from barrier 2 that received ketoprofen in the third study had gastrointestinal lesions similar to those observed in the first study, whereas none of the rats from barrier 1 had any lesions. These results suggest that the adverse effects seen after administration of ketoprofen were due to differences between barriers.