一种用于评估和治疗腰椎小关节骨关节炎所致背痛的新型动物模型的特征描述。
Characterization of a new animal model for evaluation and treatment of back pain due to lumbar facet joint osteoarthritis.
作者信息
Kim Jae-Sung, Kroin Jeffrey S, Buvanendran Asokumar, Li Xin, van Wijnen Andre J, Tuman Kenneth J, Im Hee-Jeong
机构信息
Rush University Medical Center, Chicago, Illinois 60612, USA.
出版信息
Arthritis Rheum. 2011 Oct;63(10):2966-73. doi: 10.1002/art.30487.
OBJECTIVE
Osteoarthritic (OA) degeneration of the lumbar facet joints has been implicated in low back pain. This study was undertaken to investigate the biologic links between cellular and structural alterations within facet joint components and the development of symptomatic chronic back pain.
METHODS
We generated an animal model of facet joint degeneration by intraarticular injection of monosodium iodoacetate (MIA) into facet joints (L3-L4, L4-L5, L5-L6) of Sprague-Dawley rats. Pain sensation due to pressure, which mimics a mechanical stimulus for facet joint injury, was measured using an algometer. Pain response was also assessed in a straight leg raising test. Cartilage alterations were assessed by biochemical evaluation and microfocal computed tomography (micro-CT). Therapeutic modulation of chronic facet joint pain with the use of various pharmacologic agents was investigated.
RESULTS
MIA injection resulted in severely damaged facet joint cartilage, proteoglycan loss, and alterations of subchondral bone structure. Micro-CT analyses suggested that the behavioral hyperalgesia from facet joint degeneration was not associated with foraminal stenosis. The biologic and structural changes in facet joints were closely associated with sustained and robust chronic pain. Morphine and pregabalin markedly alleviated pressure hyperalgesia, while celecoxib (a selective inhibitor of cyclooxygenase 2 [COX-2]) produced moderate antihyperalgesic effects and the effect of ketorolac (an inhibitor of COX-1 and COX-2) was negligible.
CONCLUSION
Our findings demonstrate that MIA injection provides a useful model for the study of OA changes in the facet joint and indicate that facet joint degeneration is a major cause of chronic low back pain. The treatment results suggest that classes of drugs that are widely used to treat OA, such as nonsteroidal antiinflammatory drugs, may have limited efficacy once joint destruction is complete.
目的
腰椎小关节的骨关节炎（OA）退变被认为与腰痛有关。本研究旨在探讨小关节各组成部分的细胞和结构改变与症状性慢性背痛发展之间的生物学联系。
方法
通过向Sprague-Dawley大鼠的小关节（L3-L4、L4-L5、L5-L6）内注射碘乙酸钠（MIA）建立小关节退变动物模型。使用压力痛觉计测量模拟小关节损伤机械刺激的压力引起的疼痛感觉。还通过直腿抬高试验评估疼痛反应。通过生化评估和微焦点计算机断层扫描（micro-CT）评估软骨改变。研究了使用各种药物对慢性小关节疼痛的治疗调节作用。
结果
注射MIA导致小关节软骨严重受损、蛋白聚糖丢失和软骨下骨结构改变。Micro-CT分析表明，小关节退变引起的行为性痛觉过敏与椎间孔狭窄无关。小关节的生物学和结构变化与持续且强烈的慢性疼痛密切相关。吗啡和普瑞巴林显著减轻压力性痛觉过敏，而塞来昔布（一种环氧化酶2 [COX-2] 选择性抑制剂）产生中度抗痛觉过敏作用，酮咯酸（一种COX-1和COX-2抑制剂）的作用可忽略不计。
结论
我们的研究结果表明，注射MIA为研究小关节OA变化提供了一个有用的模型，并表明小关节退变是慢性腰痛的主要原因。治疗结果表明，一旦关节破坏完成，广泛用于治疗OA的药物类别，如非甾体抗炎药，可能疗效有限。
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