Intra-articular injection of collagenase in the knee of rats as an alternative model to study nociception associated with osteoarthritis.
Intra-articular injection of collagenase in the knee of rats as an alternative model to study nociception associated with osteoarthritis.
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DOI：
10.1186/ar4436
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发表时间：
2014-01-15
影响因子：
4.9
通讯作者：
Neto FL
中科院分区：
文献类型：
--
作者：
Adães S;Mendonça M;Santos TN;Castro-Lopes JM;Ferreira-Gomes J;Neto FL
目前用于骨关节炎相关疼痛研究的动物模型不能充分再现人类骨关节炎的起始事件和结构病理学。相反，关节内注射胶原酶是一种结构相关的模型，因为它通过消化软骨中的胶原蛋白和引起关节不稳定来诱导关节变性，从而再现了与骨关节炎发作和发展相关的一些主要事件。在这里，我们评估了关节内注射胶原酶是否可以作为研究骨关节炎相关伤害感受的替代模型。通过将250 U或500 U的胶原酶两次关节内注射到成年雄性Wistar大鼠的左膝关节中来诱导骨关节炎。通过屈膝和猫步试验对运动和负荷引起的伤害性感受进行了为期六周的时间过程评估。在注射500 U胶原酶的动物中评价吗啡、利多卡因和双氯芬酸对伤害性行为的影响。在整个时间内对两种剂量的关节组织病理学进行评分。检测同侧背根神经节（DRG）瞬时受体电位香草酸1（TRPV 1）的表达。关节内注射胶原酶后，观察到与受影响关节的运动和负荷相关的伤害性行为增加。使用500 U剂量的胶原酶，6周后发生的行为学和组织病理学骨关节炎样结构变化之间存在显著相关性。注射500 U胶原酶后1周，还观察到注射的膝关节肿胀和滑膜炎症，表明发生了早期炎症反应。吗啡和利多卡因可有效逆转500 U剂量胶原酶诱导的行为变化。双氯芬酸注射后1周有效。注射500 U胶原酶后6周TRPV1表达增加。 我们的结论是，500 U的胶原酶在大鼠膝关节内注射可以是一个替代模型的研究与骨关节炎相关的伤害性感受，因为它会引起显着的伤害性改变与相关的骨关节炎样关节结构的变化。
Animal models currently used in osteoarthritis-associated pain research inadequately reproduce the initiating events and structural pathology of human osteoarthritis. Conversely, intra-articular injection of collagenase is a structurally relevant model, as it induces articular degeneration both by digesting collagen from cartilage and by causing articular instability, thereby reproducing some of the main events associated with osteoarthritis onset and development. Here, we evaluated if the intra-articular injection of collagenase can be an alternative model to study nociception associated with osteoarthritis. Osteoarthritis was induced by two intra-articular injections of either 250 U or 500 U of collagenase into the left knee joint of adult male Wistar rats. A six weeks time-course assessment of movement- and loading-induced nociception was performed by the Knee-Bend and CatWalk tests. The effect of morphine, lidocaine and diclofenac on nociceptive behaviour was evaluated in animals injected with 500 U of collagenase. Joint histopathology was scored for both doses throughout time. The expression of transient receptor potential vanilloid 1 (TRPV1) in ipsilateral dorsal root ganglia (DRG) was evaluated. An increase in nociceptive behaviour associated with movement and loading of affected joints was observed after intra-articular collagenase injection. With the 500 U dose of collagenase, there was a significant correlation between the behavioural and the histopathological osteoarthritis-like structural changes developed after six weeks. One week after injection of 500 U collagenase, swelling of the injected knee and inflammation of the synovial membrane were also observed, indicating the occurrence of an early inflammatory reaction. Behavioural changes induced by the 500 U dose of collagenase were overall effectively reversed by morphine and lidocaine. Diclofenac was effective one week after injection. TRPV1 expression increased six weeks after 500 U collagenase injection. We conclude that the intra-articular injection of 500 U collagenase in the knee of rats can be an alternative model for the study of nociception associated with osteoarthritis, since it induces significant nociceptive alterations associated with relevant osteoarthritis-like joint structural changes.
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影响因子：
4.9
作者：
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