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Intra-articular anaesthesia mitigates established pain in experimental osteoarthritis: A preliminary study of gait impulse redistribution as a biomarker of analgesia pharmacodynamics

机译:关节内麻醉可缓解实验性骨关节炎的既定疼痛:步态冲动重新分布作为镇痛药效学生物标志物的初步研究

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Objective: Develop a sensitive, functional biomarker of persistent joint pain in a large animal model of experimental osteoarthritis. Evaluate Impulse Ratio as a measure of weight distribution among supporting limbs throughout the early natural history of osteoarthritis and with local anaesthesia and analgesia. Design: The distribution of weight bearing in the trot of 11 skeletally-mature dogs was analyzed before and after unilateral surgical intervention (cranial cruciate transection or distal femoral focal impact). The short-term effects of two analgesic treatments (intra-articular lidocaine and intra-dermal meloxicam) were then evaluated as an index of pain relief based on the redistribution of weight-bearing impulse between normal and injured limbs. Results: Impulse Ratio was able to resolve weight redistribution between limbs in both long-term (weekly for over 400 days) and short-term (15min intervals) joint evaluations. Joint pain relief from lidocaine administration could be reliably tracked over its brief acting time course. Meloxicam administration resulted in ambiguous results, where average weight bearing in the injured limb did not increase, but the variability of limb use changed transiently and reversibly. Conclusion: Joint function and the role of persistent joint pain in the development of osteoarthritis can be investigated effectively and efficiently in a large animal model through the use of Impulse Ratio. Impulse Ratio can be a functionally relevant and sensitive biomarker of locomotion-related joint pain.
机译:目的:在实验性骨关节炎的大型动物模型中开发一种敏感,功能性的持续性关节痛生物标志物。评估冲动比率,作为骨关节炎早期自然史以及局部麻醉和镇痛过程中支撑四肢重量分布的度量。设计:分析了单侧手术干预(颅骨交叉横断或股骨远端局灶性撞击)前后11只骨骼成熟犬小跑的负重分布。然后,根据正常和受伤肢体之间负重冲动的重新分配,评估两种镇痛方法(关节内利多卡因和皮内美洛昔康)的短期效果,作为缓解疼痛的指标。结果:在长期(每周超过400天)和短期(每隔15分钟)的联合评估中,冲动比能够解决四肢之间的重量重新分配。在利多卡因的短暂作用过程中,可以可靠地跟踪利多卡因给药后的关节疼痛缓解情况。美洛昔康的使用导致模棱两可的结果,受伤肢体的平均承重没有增加,但是肢体使用的变异性是可逆的。结论:在大型动物模型中,通过使用脉冲比可以有效地研究关节功能和持续性关节痛在骨关节炎发展中的作用。冲动比可以是与运动有关的关节痛的功能相关且敏感的生物标志物。

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