Efficacy and Effects of High-Dose Carprofen after Plantar Incision in C57BL/6J Mice

Carprofen is a nonsteroidal antiinflammatory drug (NSAID) commonly used to control postoperative pain at 5 to 10 mg/kg once or twice a day in mice. Recent literature has suggested that higher doses of carprofen may be necessary to prevent postoperative pain in mice. We studied the efficacy and clinical safety of 3 doses of carprofen at 5 (Carp5), 25 (Carp25), and 50 (Carp50) mg/kg once a day through a plantar incision pain model, plasma carprofen levels, histopathologic evaluation, serum chemistry, CBC, and fecal occult blood testing. For the plantar incisional pain procedure, male and female C57BL/6J mice ( n = 38) were randomly assigned to 1 of 4 groups; that is, saline, Carp5, Carp25, and Carp50, and all received subcutaneous injections of the treatment drug once a day for 3 d. Mechanical and thermal hypersensitivity assessments were performed 24 h before surgery and at 2, 6, 24, 48, and 72 h afterward. Thermal analgesia of saline and Carp5 were indistinguishable from each other at all timepoints, while Carp25 and Carp50 provided thermal analgesia that were indistinguishable from each other but differed from saline and Carp5. Mechanical analgesia showed similar but more graded distinctions. One Carp50 mouse displayed acute morbidity on day 4 and was euthanized. In a separate group of mice, plasma carprofen concentration for each dose was assessed following drug administration at 2, 6, 12, and 24 h ( n = 3 per timepoint). Histopathological abnormalities were seen in 1 of 8 of Carp50 mice (neutrophilic gastritis) and in 1 of 8 of Carp25 mice (ulcerative gastritis). Mice in all carprofen treatment groups had elevated AST on chemistry and positive fecal occult blood. Our results indicate that Carp25 and Carp50 more effectively provided postoperative mechanical and thermal analgesia than did Carp5 and saline using an incisional pain model in C57BL/6 mice, although Carp50 carries more risk of gastrointestinal side effects.