Ishihara Shingo, Miller Rachel E, Malfait Anne-Marie
Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center; Chicago Center on Musculoskeletal Pain;
Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center; Chicago Center on Musculoskeletal Pain.
J Vis Exp. 2025 Jun 13(220). doi: 10.3791/68480.
Assessment of knee hyperalgesia provides a robust assay for measuring peripheral sensitization in the knee, and represents a clinically relevant pain-dependent behavior that can be used in rodent models of arthritis. Several methods have been reported to determine the threshold for responses to knee compression in rodents. Here, we aimed to adapt existing methods to develop a standardized method for assessing knee hyperalgesia in adult mice, using a Pressure Application Measurement (PAM) device. The protocol includes detailed steps, training recommendations for new experimenters, and tips for achieving consistent results. We provide suggestions for optimal training of a new experimenter. Finally, representative outcomes are provided for both acute models of transient hyperalgesia and experimental osteoarthritis (OA) models, which are characterized by chronic pain. This method is highly sensitive to pharmacological interventions, making it suitable for evaluating the effects of mediators like cytokines and for medium-throughput drug screening assays. In summary, the described approach provides a robust and clinically relevant method for quantifying knee hyperalgesia.
评估膝关节痛觉过敏为测量膝关节的外周敏化提供了一种可靠的测定方法，并且代表了一种可用于关节炎啮齿动物模型的临床相关的疼痛依赖性行为。已经报道了几种确定啮齿动物对膝关节压迫反应阈值的方法。在此，我们旨在采用现有方法，使用压力施加测量（PAM）装置开发一种用于评估成年小鼠膝关节痛觉过敏的标准化方法。该方案包括详细步骤、针对新实验者的培训建议以及获得一致结果的提示。我们为新实验者的最佳培训提供建议。最后，给出了短暂性痛觉过敏急性模型和以慢性疼痛为特征的实验性骨关节炎（OA）模型的代表性结果。该方法对药理干预高度敏感，使其适用于评估细胞因子等介质的作用以及用于中等通量药物筛选试验。总之，所描述的方法为量化膝关节痛觉过敏提供了一种可靠且临床相关的方法。
