CNS Research, Orion Corporation Orion Pharma, Turku, Finland; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
CNS Research, Orion Corporation Orion Pharma, Turku, Finland.
J Neurosci Methods. 2018 Apr 15;300:92-102. doi: 10.1016/j.jneumeth.2017.04.011. Epub 2017 Apr 24.
There is a need for better joint pain treatment, but development of new medication has not been successful. Pre-clinical models with readouts that better reflect the clinical situation are needed. In patients with joint pain, pain at rest and pain at walking are two major complaints.
We describe a new way of calculating results from gait analysis using the CatWalk™ setup. Rats with monoarthritis induced by injection of Complete Freund's Adjuvant (CFA) intra-articularly into the ankle joint of one hind limb were used to assess gait and dynamic weight bearing.
The results show that dynamic weight bearing was markedly reduced for the injected paw. Gait parameters such as amount of normal step sequences, walking speed and duration of step placement were also affected. Treatment with naproxen (an NSAID commonly used for inflammatory pain) attenuated the CFA-induced effects. Pregabalin, which is used for neuropathic pain, had no effect.
Reduced dynamic weight bearing during locomotion, assessed and calculated in the way we present here, showed a dose-dependent and lasting normalization after naproxen treatment. In contrast, static weight bearing while standing (Incapacitance tester) showed a significant effect for a limited time only. Mechanical sensitivity (von Frey Optihairs) was completely normalized by naproxen, and the window for testing pharmacological effect disappeared.
Objective and reproducible effects, with an endpoint showing face validity compared to pain while walking in patients with joint pain, are achieved by a new way of calculating dynamic weight bearing in monoarthritic rats.
需要更好的关节痛治疗方法,但新药物的开发尚未成功。需要具有更好地反映临床情况的读出结果的临床前模型。在有关节痛的患者中,静息时疼痛和行走时疼痛是两个主要的抱怨。
我们描述了一种使用 CatWalk™ 设备计算步态分析结果的新方法。通过向一只后肢踝关节内注射完全弗氏佐剂(CFA)来诱导关节炎的大鼠用于评估步态和动态负重。
结果表明,注射侧的负重明显减少。步态参数,如正常步序列的数量、行走速度和步放置持续时间也受到影响。用萘普生(一种常用于治疗炎症性疼痛的 NSAID)治疗可减轻 CFA 引起的影响。用于治疗神经病理性疼痛的普瑞巴林则没有效果。
我们提出的这种新方法评估和计算的运动中动态负重减少,在萘普生治疗后表现出剂量依赖性和持久的正常化。相比之下,站立时的静态负重(Incapacitance 测试仪)仅在有限的时间内有显著效果。机械敏感性(von Frey Optihairs)完全被萘普生正常化,并且测试药理作用的窗口消失了。
通过一种新的方法计算单关节炎大鼠的动态负重,可实现具有与患者行走时疼痛相比具有直观有效性的客观和可重复的效果,以及具有终点的检测功效。