Departments of Physical Medicine & Rehabilitation, Orthopedic Surgery, and Biochemistry, Rush University Medical Center, Chicago, IL, USA.
PM R. 2011 Jun;3(6 Suppl 1):S88-94. doi: 10.1016/j.pmrj.2011.04.020.
Low back pain carries an enormous socioeconomic burden. Current treatment modalities for symptomatic intervertebral disk (IVD) degeneration have limited and often inconsistent clinical benefits. Novel approaches with the potential to halt or even reverse disk degeneration and restore physiologic disk function, such as biological treatments, are therefore very attractive. The following barriers are impeding the development of successful therapeutic interventions: (1) the biology and pathophysiology of disk degeneration are not well understood, and (2) the precise relationship between IVD degeneration and low back pain remains unclear. This article reviews the structural changes that take place during IVD degeneration and their relationship to diskogenic back pain. It also presents treatment modalities that currently are under laboratory investigation and are being studied in clinical trials. The authors of recent studies have shown that the content of large proteoglycans, such as aggrecan and versican, decreases with aging and IVD degeneration, whereas the content of certain small proteoglycans, such as biglycan, increases. Proinflammatory cytokines such as interleukin-1 and tumor necrosis factor-α also are associated with IVD degeneration and are potential biomarkers of IVD degeneration and repair. Our group of investigators and others have developed in vitro models of IVD cell and explant culture in addition to in vivo animal models to study IVD degeneration and repair. With the use of these models, we have tested candidate therapeutic agents to assess their therapeutic potential for matrix restoration. When a rabbit annular puncture model of IVD degeneration was used, injections of either bone morphogenetic protein-7 (also known as osteogenic protein-1) or bone morphogenetic protein-14 (also known as growth differentiation factor-5) were shown to be effective in restoring IVD structures. On the basis of these data, the Food and Drug Administration has recently allowed the initiation of Investigational New Drug clinical trials on osteogenic protein-1 and growth differentiation factor-5 in the United States. Protein therapies such as other growth factors, inhibitors of degradation enzymes or cytokines, and cell therapies also are being investigated in laboratory settings with the goal of restoring disk function and alleviating back pain symptoms. These therapies may be used by physiatrists with the skills required to administer intradiskal injections and supervise a comprehensive rehabilitation program after the procedures. Ultimately, the clinical use of any biological treatment discussed in this article would require the collective efforts of clinicians and researchers.
下背痛带来了巨大的社会经济负担。目前对有症状的椎间盘（IVD）退变的治疗方法疗效有限，且往往不一致。因此，具有阻止甚至逆转椎间盘退变并恢复生理椎间盘功能的新方法，如生物治疗，非常有吸引力。以下障碍阻碍了成功治疗干预措施的发展：（1）椎间盘退变的生物学和病理生理学尚不清楚，（2）IVD 退变与下腰痛之间的精确关系尚不清楚。本文综述了 IVD 退变过程中的结构变化及其与椎间盘源性腰痛的关系。还介绍了目前正在实验室研究并正在临床试验中研究的治疗方法。最近研究的作者表明，随着年龄的增长和 IVD 退变，大型蛋白聚糖（如聚集蛋白聚糖和 versican）的含量减少，而某些小蛋白聚糖（如 biglycan）的含量增加。白细胞介素 1 和肿瘤坏死因子-α等促炎细胞因子也与 IVD 退变有关，是 IVD 退变和修复的潜在生物标志物。我们的研究小组和其他研究小组除了建立体内动物模型外，还建立了体外椎间盘细胞和外植体培养模型，以研究 IVD 退变和修复。使用这些模型，我们已经测试了候选治疗药物，以评估它们对基质恢复的治疗潜力。当使用兔椎间盘环穿刺模型时，发现骨形态发生蛋白-7（也称为骨形成蛋白-1）或骨形态发生蛋白-14（也称为生长分化因子-5）的注射均有效恢复 IVD 结构。基于这些数据，食品和药物管理局最近允许在美国开始骨形成蛋白-1 和生长分化因子-5 的新药临床试验。蛋白质疗法，如其他生长因子、降解酶或细胞因子抑制剂，以及细胞疗法，也正在实验室环境中进行研究，目的是恢复椎间盘功能并缓解腰痛症状。这些治疗方法可能由具备进行椎间盘内注射所需技能的物理治疗师使用，并在手术后监督全面的康复计划。最终，本文讨论的任何生物治疗的临床应用都需要临床医生和研究人员的共同努力。
