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我们能从伴侣动物的骨关节炎疼痛中学到什么?

What can we learn from osteoarthritis pain in companion animals?

作者信息

Cimino Brown Dorothy

机构信息

Translational Comparative Medical Research, Elanco Animal Health, Greenfield, NI, USA.

出版信息

Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 107(5):53-58. Epub 2017 Sep 29.

Abstract

The lack of successful translation of basic research discoveries into safe and effective treatments for chronic pain patients has led to increased scrutiny of the preclinical models used in pain research, particularly for osteoarthritis, where there is a significant disconnect between the animal models used to study the structural versus symptomatic aspects of the disease. Companion dogs offer a unique opportunity to assess osteoarthritis pain in a physiologically relevant 'model' of the disease. Approximately 20% of the canine pet population spontaneously develops osteoarthritis, translating to at least 15 million dogs in the United States alone. As in humans, pathogenesis of canine osteoarthritis involves changes in all tissues of the synovial joint including articular cartilage, subchondral bone, and periosteum. The dominant symptom of osteoarthritis for both humans and dogs is pain, and the current therapeutic goal for both species is management of that pain and associated loss of function. To capture clinically and translationally relevant pain severity and pain impact data in the companion canine osteoarthritis 'model', clinical metrology instruments have been validated. These instruments, which assess changes in spontaneous pain-related behaviours, over extended periods of time, in the dog's home environment, are used to evaluate the efficacy of novel interventions for chronic pain in canine osteoarthritis studies. There is evidence that these results in companion dogs can reliably predict efficacy in humans. Across many classes of compounds in which there have been studies in companion animal chronic pain conditions and the same conditions in humans, the analogous results have been seen. In addition, many of the drugs used to treat pain in people are successfully used off-label to treat pain in dogs as well. If preliminary indications of predictability hold true, companion dogs may be embraced as a missing link in the translation of osteoarthritis treatment from mice to men.

摘要

基础研究成果未能成功转化为针对慢性疼痛患者的安全有效治疗方法,这导致对疼痛研究中使用的临床前模型的审查日益严格,尤其是骨关节炎方面,用于研究该疾病结构与症状方面的动物模型之间存在显著脱节。伴侣犬为在与疾病生理相关的“模型”中评估骨关节炎疼痛提供了独特机会。大约20%的犬类宠物会自发患上骨关节炎,仅在美国就有至少1500万只狗患病。与人类一样,犬类骨关节炎的发病机制涉及滑膜关节所有组织的变化,包括关节软骨、软骨下骨和骨膜。人类和犬类骨关节炎的主要症状都是疼痛,目前这两个物种的治疗目标都是控制疼痛及相关功能丧失。为在伴侣犬骨关节炎“模型”中获取临床和转化相关的疼痛严重程度及疼痛影响数据,临床计量工具已得到验证。这些工具用于评估在犬类家庭环境中长时间内与自发疼痛相关行为的变化,以评估犬类骨关节炎研究中新型慢性疼痛干预措施的疗效。有证据表明,伴侣犬的这些结果能够可靠地预测对人类的疗效。在许多已在伴侣动物慢性疼痛状况及人类相同状况下进行研究的化合物类别中,都观察到了类似结果。此外,许多用于治疗人类疼痛的药物也成功地被用于非标签治疗犬类疼痛。如果预测性的初步迹象成立,伴侣犬可能会被视为骨关节炎治疗从小鼠到人类转化过程中缺失的一环。

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