Faculty of Veterinary Medicine, Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, Canada.
Pharmacol Biochem Behav. 2011 Jan;97(3):603-10. doi: 10.1016/j.pbb.2010.11.003. Epub 2010 Nov 25.
The purpose of this study was to compare the gait parameters recorded on the CatWalk and the mechanical sensitivity with von Frey filaments of two putative models of osteoarthritis over a one month period, and to evaluate the effect of celecoxib on these parameters. Animals underwent either a surgical sectioning of the anterior cruciate ligament with partial medial menisectomy (ACLT+pMMx) to create a joint instability model or received an intra-articular injection of monoiodoacetate (MIA) as a putative inflammatory joint pain model. Animals were assessed for four consecutive weeks and knee joints were then evaluated histologically. Spinal cord lumbar enlargements were harvested for selected neuropeptide analysis (substance P (SP) and calcitonin gene related peptide (CGRP)). With the MIA model, significant changes persisted in selected dynamic gait parameters throughout the study in the injured limb as well as with the von Frey filaments. The ACLT+pMMx model in contrast showed no clear differential response between both hind limb for both gait parameters and pain-related behavior with von Frey filaments occurred only on the last day of the study. Neuropeptide analysis of spinal cord lumbar enlargements revealed a significant increase in CGRP concentration in both models and an increase in SP concentration only in the MIA model. Histological evaluation confirmed the presence of articular cartilage lesions in both models, but they were much more severe in the MIA model. Celecoxib had an effect on all selected gait parameters at the very beginning of the study and had an important alleviating effect on mechanical allodynia. These results suggest that the MIA model may be more appropriate for the evaluation of short term pain studies and that celecoxib may modulate mechanical allodynia through central sensitization mechanisms.
本研究的目的是比较 CatWalk 记录的步态参数和机械敏感性与 von Frey 纤维丝在一个月期间两种潜在骨关节炎模型，以及评价塞来昔布对这些参数的影响。动物接受了前交叉韧带横断术加部分内侧半月板切除术（ACLT+pMMx）造成关节不稳模型或关节内注射单碘乙酸（MIA）造成潜在炎性关节痛模型。动物连续 4 周评估，然后评估膝关节组织学。选择神经肽分析（P 物质（SP）和降钙素基因相关肽（CGRP））时收集脊髓腰膨大。MIA 模型中，在研究过程中，受伤肢体的选定动态步态参数和 von Frey 纤维丝都持续发生显著变化。相比之下，ACLT+pMMx 模型在步态参数和 von Frey 纤维丝引起的疼痛相关行为方面，两后肢之间没有明显的差异反应，仅在研究的最后一天才出现。脊髓腰膨大神经肽分析显示两种模型的 CGRP 浓度均显著增加，仅在 MIA 模型中 SP 浓度增加。组织学评估证实两种模型均存在关节软骨损伤，但 MIA 模型更为严重。塞来昔布在研究开始时对所有选定的步态参数均有影响，对机械性痛觉过敏有重要缓解作用。这些结果表明，MIA 模型可能更适合短期疼痛研究的评价，塞来昔布可能通过中枢敏化机制调节机械性痛觉过敏。
