Behavioral signs of pain and functional impairment in a mouse model of osteogenesis imperfecta
Behavioral signs of pain and functional impairment in a mouse model of osteogenesis imperfecta
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DOI：
10.1016/j.bone.2015.08.001
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发表时间：
2015-12-01
期刊：
影响因子：
4.1
通讯作者：
Stone, Laura S.
中科院分区：
文献类型：
--
作者：
Abdelaziz, Dareen M.;Abdullah, Sami;Stone, Laura S.
成骨不全症（OI）是一种先天性疾病，通常由编码I型胶原α链的COL1A1或COL1A2基因的显性突变引起。严重的成骨不全与骨骼畸形和频繁骨折有关。骨痛可在骨折后急性发作，但也可在没有骨折前慢性发作。在这项研究中，我们评估了Col1a1Jrt/+小鼠的OI相关疼痛，Col1a1Jrt/+小鼠是最近开发的一种严重显性OI模型。与人类严重的成骨不全类似，这只老鼠有明显的骨骼异常，并发生自发性骨折、关节脱位和椎体畸形。在这个模型中，我们研究了疼痛和功能损伤的行为测量。与对照野生型幼崽相比，在成骨不全症中观察到对机械、热和冷刺激的显著超敏反应，分别通过von Frey丝、辐射热爪退出和丙酮试验进行了评估。成骨不全小鼠在滚轮和开阔场地试验中也表现出运动活动减少。免疫细胞化学分析显示，OI和WT小鼠后肢无毛皮肤的神经支配和感觉神经元中疼痛相关神经肽降钙素基因相关蛋白的表达没有变化。相反，对机械和冷刺激的敏感性增加与成骨不全小鼠骨骼畸形的程度密切相关。因此，我们证明Col1a1Jrt/+严重成骨不全小鼠模型对机械和热刺激过敏，与慢性疼痛状态一致。(C) 2005爱思唯尔公司版权所有。
Osteogenesis imperfecta (OI) is a congenital disorder caused most often by dominant mutations in the COL1A1 or COL1A2 genes that encode the alpha chains of type I collagen. Severe forms of OI are associated with skeletal deformities and frequent fractures. Skeletal pain can occur acutely after fracture, but also arises chronically without preceding fractures. In this study we assessed OI-associated pain in the Col1a1Jrt/+ mouse, a recently developed model of severe dominant OI. Similar to severe OI in humans, this mouse has significant skeletal abnormalities and develops spontaneous fractures, joint dislocations and vertebral deformities. In this model, we investigated behavioral measures of pain and functional impairment. Significant hypersensitivity to mechanical, heat and cold stimuli, assessed by von Frey filaments, radiant heat paw withdrawal and the acetone tests, respectively, were observed in OI compared to control wildtype littermates. OI mice also displayed reduced motor activity in the running wheel and open field assays. Immunocytochemical analysis revealed no changes between OI and WT mice in innervation of the glabrous skin of the hindpaw or in expression of the pain-related neuropeptide calcitonin gene-related protein in sensory neurons. In contrast, increased sensitivity to mechanical and cold stimulation strongly correlated with the extent of skeletal deformities in OI mice. Thus, we demonstrated that the Col1a1Jrt/+ mouse model of severe OI has hypersensitivity to mechanical and thermal stimuli, consistent with a state of chronic pain. (C) 2OI5 Elsevier Inc. All rights reserved.