Department of Experimental Biology, Faculty of Medicine of Porto and IBMC-Institute for Molecular and Cell Biology, University of Porto, Alameda Prof. Hernani Monteiro, 4200 Porto, Portugal.
Pharmacol Biochem Behav. 2012 Jun;101(4):617-24. doi: 10.1016/j.pbb.2012.03.003. Epub 2012 Mar 9.
Pain is the major symptom of osteoarthritis (OA) and the main reason for patients seeking medical care, but its treatment is not optimal. Animal studies are necessary to elucidate mechanisms underlying OA-induced pain and assess analgesics' efficacy. Previously, we showed that the Knee-Bend test and dynamic weight bearing by the CatWalk test are clinically relevant methods for assessing movement-induced nociception in the mono-iodoacetate (MIA) OA model. Using the same tests, in the present study we investigate the effects of lidocaine (5 mg, 10% solution, intra-articular), morphine (6 mg/kg, subcutaneous) and diclofenac (30 mg/kg per os) on nociceptive behavior in OA animals, on days 3 and 20 of OA evolution. Morphine reduced nociceptive behavior in both tests at both time-points. Lidocaine also decreased nociceptive behavior in both tests on day 3, but on day 20 only reduced the Knee-Bend score. Diclofenac was highly effective in both tests on day 3, while on day 20 it induced a less pronounced decrease in the Knee-Bend score and was ineffective in the CatWalk test. The results showed that the Knee-Bend and CatWalk tests are reliable alternative methods for evaluating movement-induced nociception in OA animals, and measure nociception in a clinically relevant way, since an analgesic profile similar to the one described in humans was observed. Therefore, these tests might be important as good predictors of drug efficacy.
疼痛是骨关节炎（OA）的主要症状，也是患者寻求医疗的主要原因，但疼痛的治疗效果并不理想。动物研究对于阐明 OA 引起的疼痛机制以及评估镇痛药的疗效是必要的。此前，我们已经证明，在单碘乙酸（MIA）OA 模型中，膝关节弯曲试验（Knee-Bend test）和 CatWalk 试验的动态负重测试是评估运动引起的伤害感受的临床相关方法。在本研究中，我们使用相同的测试，研究了利多卡因（5mg，10%溶液，关节内注射）、吗啡（6mg/kg，皮下注射）和双氯芬酸（30mg/kg，口服）对 OA 动物疼痛行为的影响，分别在 OA 发展的第 3 天和第 20 天。吗啡在这两种测试中均在两个时间点降低了疼痛行为。利多卡因在第 3 天的两种测试中也降低了疼痛行为，但在第 20 天仅降低了膝关节弯曲评分。双氯芬酸在第 3 天的两种测试中均非常有效，而在第 20 天，它仅降低了膝关节弯曲评分，而在 CatWalk 测试中无效。结果表明，膝关节弯曲和 CatWalk 测试是评估 OA 动物运动引起的伤害感受的可靠替代方法，并且以临床相关的方式测量伤害感受，因为观察到与人类描述相似的镇痛谱。因此，这些测试可能是预测药物疗效的重要指标。
