Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan;, Email:
Unit for Laboratory Animal Medicine, Refinement and Enrichment Advancements Laboratory (REAL), University of Michigan Medical School, Ann Arbor, Michigan.
J Am Assoc Lab Anim Sci. 2018 May 1;57(3):258-267.
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.
非甾体抗炎药（NSAID）类镇痛药可能会干扰需要炎症来模拟人类疾病发展的模型。这一影响给兽医工作人员和研究人员带来了挑战，因为手术通常是创建疾病的小鼠模型所必需的，而 NSAID 是用于治疗术后疼痛的一线镇痛药。我们评估了罗非昔布（一种高度选择性环氧化酶 2 的 NSAID）在角叉菜胶足肿胀（CPE）测定和静脉血栓形成（VT）手术模型中的作用。我们通过使用 CPE 测定法生成了罗非昔布剂量为 3.2、10、32 和 100mg/kg SC 的小鼠特异性剂量反应曲线。电子von Frey 测定法、卡尺和用于测量旷场活动的新型软件显示，与生理盐水相比，所有罗非昔布剂量均在 3 和 6 小时时提供了有效的镇痛作用。此外，100mg/kg 剂量具有可测量的抗炎作用，但产生了可测量的临床副作用。由于 32mg/kg 剂量是最高的镇痛剂量，不会减少足肿胀，因此我们在相同的伤害感受和行为测定法中进一步评估了该剂量，此外还评估了新型巢巩固测试以及手术 VT 模型中的血栓形成和血液学参数。单次预先给予 32mg/kg SC 罗非昔布或 5mg/kg SC 卡洛芬可预防 24 和 48 小时时的继发性痛觉过敏。两种药物均未改变 VT 模型中的血栓形成或血液学值。旷场活动软件和我们的新型巢巩固测试均识别出明显的术后不适，但无法区分生理盐水和镇痛组。鉴于这些数据，单次预先给予 32mg/kg SC 罗非昔布或 5mg/kg SC 卡洛芬的皮下剂量不会阻碍这种 VT 模式，但也未能提供足够的术后镇痛。
