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豚鼠和大鼠两种关节炎模型中疼痛行为与骨质破坏的评估

Evaluation of pain behavior and bone destruction in two arthritic models in guinea pig and rat.

作者信息

Vermeirsch Hilde, Biermans Ria, Salmon Philip L, Meert Theo F

机构信息

CNS Pain & Neurology, J&J Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.

出版信息

Pharmacol Biochem Behav. 2007 Aug-Sep;87(3):349-59. doi: 10.1016/j.pbb.2007.05.010. Epub 2007 May 23.

Abstract

The primary aim of the study was to describe and correlate pain behavior and changes in bone morphology in animal models of arthritis both in rats and guinea pigs. Either complete Freund's adjuvant (CFA) or mono-iodoacetate (MIA) solution was injected into the left knee joint to obtain a model for rheumatoid arthritis and osteoarthritis, respectively. Subsequently, animals were behaviorally tested during a period of 12 days after CFA injection and at least 19 days after MIA injection. During these observation periods increasing pain behavior was observed, characterized by decreased von Frey mechanical thresholds and weight bearing on the affected limb. In Hargreaves' paw flick test slightly increased thermal hypersensitivity was observed in some instances in guinea pigs. In rats there was also decreased limb-use during forced ambulation. To evaluate bone destruction mu-computed tomography scans of the arthritic knee were taken on the last experimental day. Different bone parameters indicative of osteolysis and decreased trabecular connectivity were significantly correlated with the observed pain behavior. Detailed description of morphological changes in arthritic joints better characterizes the different animal models and might add to the knowledge on the working mechanisms of analgesic compounds that have an influence on bone structures in arthritis.

摘要

该研究的主要目的是描述和关联大鼠和豚鼠关节炎动物模型中的疼痛行为与骨形态变化。分别向左膝关节注射完全弗氏佐剂(CFA)或单碘乙酸盐(MIA)溶液,以分别获得类风湿性关节炎和骨关节炎模型。随后,在注射CFA后的12天内以及注射MIA后至少19天对动物进行行为测试。在这些观察期内,观察到疼痛行为增加,其特征为von Frey机械阈值降低以及患侧肢体负重减少。在哈格里夫斯(Hargreaves)爪轻弹试验中,在某些豚鼠中观察到热超敏反应略有增加。在大鼠中,强迫行走时肢体使用也减少。为了评估骨破坏情况,在实验的最后一天对关节炎膝关节进行了微计算机断层扫描。指示骨溶解和小梁连接性降低的不同骨参数与观察到的疼痛行为显著相关。对关节炎关节形态变化的详细描述能更好地表征不同的动物模型,并可能增加对影响关节炎骨结构的镇痛化合物作用机制的了解。

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