Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate
Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate
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DOI：
10.1016/j.joca.2016.02.006
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发表时间：
2016-07-01
影响因子：
7
通讯作者：
Takamatsu, H.
中科院分区：
文献类型：
--
作者：
Ogawa, S.;Awaga, Y.;Takamatsu, H.
目的：一些有前途的化合物开发骨关节炎疼痛未能证明临床疗效。为了加强骨关节炎的临床前转化研究，研究人员在Macaca Macaca fascularis身上建立了一个膝关节骨关节炎疼痛模型，并测试了两种不同药理类别的药物对疼痛相关行为的影响。设计：行为评估是专门为猕猴开发的。在单侧内侧半月板切除术（MMx）前评估基线膝关节压力阈值和负重。在服用MMx 15天后，猕猴接受了为期36天的每天一次的锻炼方案。MMx后67天，猕猴被分配到三个治疗组中的一个（n = 3/组），非甾体抗炎药（NSAID）双氯芬酸，NK1受体拮抗剂阿瑞吡坦或对照物，治疗5天。动物在给药后3-4小时进行盲法测试。治疗采用交叉设计，每只动物接受所有治疗，治疗之间使用9天的洗脱期。结果：给药的猕猴一致表现出同侧压力阈值降低（痛觉过敏）和体重减轻。虽然双氯芬酸增加了负重和压力阈值，但没有得到疼痛的完全衰减。阿瑞吡坦对膝关节压力和负重均无显著改善。结论：猕猴单侧MMx引起疼痛相关行为和膝关节病理，使人联想到骨关节炎。行为终点对NSAID治疗敏感，但对NK1受体阻断不敏感，这与临床发现相似。目前的猕猴骨关节炎模型可以用来测试骨关节炎疼痛的潜在治疗方法。(C) 2016国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: A number of promising compounds developed for osteoarthritic pain have failed to demonstrate clinical efficacy. To enhance preclinical translational research for osteoarthritis, a model of knee osteoarthritis pain was developed in Macaca fascicularis and the effects of two distinct pharmacological classes of drugs were tested on pain-related behavior.Design: Behavioral assessments were developed specifically for the macaque. Baseline knee pressure threshold and weight bearing were assessed prior to a unilateral medial meniscectomy (MMx). Fifteen days following MMx, macaques underwent a once daily exercise regimen for 36 days. Sixty-seven days following MMx, macaques were assigned to one of three treatment groups (n = 3/group), either nonsteroidal anti-inflammatory drug (NSAID) diclofenac, NK1 receptor antagonist aprepitant or vehicle, and treated for 5 days. Animals were tested 3-4 h after p.o. dosing and testing was performed blinded. Treatment utilized a crossover designdeach animal received all treatmentsdand a 9-day washout period was utilized between treatments.Results: Vehicle-treated macaques consistently demonstrated decreased ipsilateral pressure threshold ("hyperalgesia") and decreased weight bearing. While diclofenac increased weight bearing and pressure threshold, full attenuation of pain was not obtained. No significant improvement of either knee pressure or weight bearing was observed with aprepitant.Conclusions: Unilateral MMx in the macaque evoked pain-related behaviors and knee joint pathology reminiscent of osteoarthritis. The behavioral endpoints were sensitive to NSAID treatment but not sensitive to NK1 receptor block, which parallel clinical findings. The current macaque osteoarthritis model could be used to test potential treatments for osteoarthritis pain. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.