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影响啮齿类动物骨关节炎模型行为评估可靠性的因素。

Factors affecting the reliability of behavioral assessments for rodent osteoarthritis models.

机构信息

J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, USA.

出版信息

Lab Anim. 2020 Aug;54(4):317-329. doi: 10.1177/0023677219867715. Epub 2019 Aug 20.

Abstract

The translational value of osteoarthritis (OA) models is often debated because numerous studies have shown that animal models frequently fail to predict the efficacy of therapies in humans. In part, this failing may be due to the paucity of preclinical studies that include behavioral assessments in their metrics. Behavioral assessments of animal OA models can provide valuable data on the pain and disability associated with disease-sequelae of significant clinical relevance. Clinical definitions of efficacy for OA therapeutics often center on their palliative effects. Thus, the widespread inclusion of behaviors indicative of pain and disability in preclinical animal studies may contribute to greater success identifying clinically relevant interventions. Unfortunately, studies that include behavioral assays still frequently encounter pitfalls in assay selection, protocol consistency, and data/methods transparency. Targeted selection of behavioral assays, with consideration of the array of clinical OA phenotypes and the limitations of individual behavioral assays, is necessary to identify clinically relevant outcomes in OA animal models appropriately. Furthermore, to facilitate accurate comparisons across research groups and studies, it is necessary to improve the transparency of methods. Finally, establishing agreed-upon and clear definitions of behavioral data will reduce the convolution of data both within and between studies. Improvement in these areas is critical to the continued benefit of preclinical animal studies as translationally relevant data in OA research. As such, this review highlights the current state of behavioral analyses in preclinical OA models.

摘要

骨关节炎 (OA) 模型的转化价值经常受到争议,因为许多研究表明,动物模型经常无法预测治疗方法在人类中的疗效。在某种程度上,这种失败可能是由于缺乏将行为评估纳入其指标的临床前研究。对动物 OA 模型的行为评估可以提供与疾病后遗症相关的疼痛和残疾的有价值的数据,这些疾病后遗症具有重要的临床相关性。OA 治疗药物的临床疗效定义通常集中在其缓解疼痛的作用上。因此,在临床前动物研究中广泛纳入表明疼痛和残疾的行为可能有助于更成功地确定具有临床相关性的干预措施。不幸的是,包括行为测定的研究在测定选择、方案一致性和数据/方法透明度方面仍然经常遇到陷阱。有必要有针对性地选择行为测定,考虑到各种临床 OA 表型和个体行为测定的局限性,以适当识别 OA 动物模型中的临床相关结局。此外,为了促进研究小组和研究之间的准确比较,有必要提高方法的透明度。最后,建立行为数据的公认和明确定义将减少研究内和研究间数据的复杂性。这些领域的改进对于临床前动物研究作为 OA 研究中具有转化相关性的数据的持续受益至关重要。因此,本综述强调了临床前 OA 模型中行为分析的现状。

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