Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL/6 mice
Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL/6 mice
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DOI：
10.1016/j.pain.2011.09.007
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发表时间：
2012-02-01
期刊：
影响因子：
7.4
通讯作者：
Bevan, Stuart
中科院分区：
文献类型：
--
作者：
Knights, Chancie Bayer;Gentry, Clive;Bevan, Stuart
骨关节炎（OA）的小鼠模型为阐明OA疼痛的机制提供了潜在的有力工具。然而，很少有研究检测小鼠相关OA模型的疼痛行为。因此，我们表征了部分内侧半月板切除术诱导的C57Bl/6小鼠OA模型中疼痛相关行为的时间过程和药理学敏感性。进行性退行性关节损伤以时间依赖性的方式发展，并在手术后4周首次检测到。术后12周，通过监测负重、机械性痛觉过敏、冷异常性痛、机械性异常性痛和膝关节受压发声来评估疼痛。在研究过程中没有观察到明显的负重缺陷。术后9周，同侧后肢出现明显的机械异常性疼痛。后肢机械性痛觉过敏和冷异常性痛，以及膝关节受压引起的发声增加在同侧肢体中分两个阶段发生。超敏反应的早期阶段持续了长达3周，并通过非甾体抗炎药双氯芬酸治疗得以逆转。疼痛缓解数周后，术后7周出现第二阶段非甾体抗炎药不敏感疼痛。在这个阶段，吗啡可以逆转所有的疼痛行为。相比之下，其他镇痛药物（扑热息痛、加巴喷丁和曲马多）仅对1或2种方式有选择性作用。第二阶段疼痛水平波动，有短暂的疼痛减轻。在这些时候，潜在的超敏反应可以通过纳洛酮的施用来揭示，这表明疼痛的减轻是由于内源性阿片类药物。(C) 2011年国际疼痛研究协会。Elsevier b.v.版权所有。
Murine models of osteoarthritis (OA) provide a potentially powerful tool to elucidate mechanisms responsible for OA pain. However, few studies have examined pain behaviours in relevant OA models in mice. We have therefore characterized the time course and pharmacological sensitivities of painrelated behaviours in a model of OA in C57Bl/6 mice induced by partial medial meniscectomy. Progressive degenerative joint damage developed in a time-dependent manner and was first detected 4 weeks after surgery. Pain was assessed by monitoring weight bearing, mechanical hyperalgesia, cold allodynia, mechanical allodynia and vocalisation in response to knee compression for 12 weeks postsurgery. No significant weight-bearing deficits were observed during the course of the study. Significant mechanical allodynia was present in the ipsilateral hind limb from 9 weeks after surgery. Hind limb mechanical hyperalgesia and cold allodynia, and increased vocalisation in response to knee compression developed in the ipsilateral limb in 2 phases. An early phase of hypersensitivities lasted for up to 3 weeks and was reversed by treatment with a nonsteroidal anti-inflammatory drug (NSAID), diclofenac. Pain then resolved for several weeks, followed by a second phase of NSAID-insensitive pain after 7 weeks postsurgery. During this phase, all pain behaviours could be reversed by morphine. In contrast, other analgesic drugs (paracetamol, gabapentin, and tramadol) had selective effects on only 1 or 2 modalities. Pain levels fluctuated during the second phase, with transient periods of reduced pain. At these times, underlying hypersensitivities could be unmasked by administration of naloxone, indicating that reduced pain was due to endogenous opioids. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.