Analgesic Efficacy and Hematologic Effects of Robenacoxib in Mice

• Published in: Journal of the American Association for Laboratory Animal Science 2018-05, Vol.57 (3), p.258-267
• Main Authors: Beninson, Jennifer A, Lofgren, Jennifer L, Lester, Patrick A, Hileman, Madeline M, Berkowitz, Daniel J, Myers Jr, Daniel D
• Format: Article
• Language: English
• Subjects: Analgesics - administration & dosage; Analgesics - pharmacology; Anesthesia; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Carbazoles; Diphenylamine - analogs & derivatives; Diphenylamine - pharmacology; Dose-Response Relationship, Drug; Female; Inflammation - drug therapy; Laboratory Animal Science; Male; Mice; Pain Management; Pain, Postoperative - drug therapy; Pain, Postoperative - veterinary; Phenylacetates - pharmacology
• ISSN: 1559-6109; 2769-6677; 2769-6677

NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease and NSAID are first-line analgesics used to treat postoperative pain. We evaluated robenacoxib, a NSAID highly selective for cyclooxygenase 2, in a carrageenan paw edema (CPE) assay and surgical model of venous thrombosis (VT). We generated a mouse-specific dose-response curve by using the CPE assay for robenacoxib doses of 3.2, 10, 32 and 100 mg/kg SC. Electronic von Frey assay, calipers, and novel software for measuring open-field activity revealed that all robenacoxib doses provided, identified effective analgesia at 3 and 6 h, compared with saline. In addition, the 100-mg/kg dose had measurable antiinflammatory effects but yielded adverse clinical side effects. Because the 32-mg/kg dose was the highest analgesic dose that did not decrease paw swelling, we evaluated it further by using the same nociceptive and behavioral assays in addition to a novel nest-consolidation test, and assessment of blood clotting and hematologic parameters in the surgical VT model. A single preemptive dose of either 32 mg/kg SC robenacoxib or 5 mg/kg SC carprofen protected against secondary hyperalgesia at 24 and 48 h. Neither drug altered clot formation or hematology values in the VT model. The open-field activity software and our novel nest consolidation test both identified significant postoperative discomfort but did not differentiate between saline and analgesia groups. In light of these data, a single preemptive subcutaneous dose of 32 mg/kg of robenacoxib or 5 mg/kg of carprofen did not impede this VT mode but also failed to provide sufficient postoperative analgesia.