PDF(Pubmed)
Abstract：
Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.
摘要：
椎间盘（IVD）变性引起的慢性腰痛，也称为慢性椎间盘源性下腰痛（CD-LBP），是最常见的肌肉骨骼疾病之一。IVD中的退化过程，如炎症和细胞外基质分解，导致神经营养蛋白释放。局部升高的神经营养蛋白水平将刺激感觉神经元的发芽和神经支配。此外，直接连接到相邻背根神经节的发芽的感觉神经已显示出增加小胶质细胞激活，有助于疼痛的维持和慢性化。目前的疼痛治疗已经表明对于长期使用是不足的或不充分的。此外，大多数针对椎间盘退变潜在发病机制的治疗方法侧重于修复和再生，而忽略了慢性疼痛。生物分子疗法如何影响退行性IVD环境，疼痛信号级联，感觉神经元的神经支配和兴奋性通常仍不清楚。这篇综述讨论了CD-LBP慢性疼痛治疗相对不足的领域，并总结了针对CD-LBP的治疗效果，特别强调慢性疼痛。已经显示基于阻断促炎介质或神经营养蛋白活性的方法阻碍神经元向内生长到椎间盘中。此外，细胞外基质成分或移植的间充质干细胞的组织再生和神经抑制特性是潜在的有趣的生物分子方法，不仅可以阻断IVD变性，还可以阻止疼痛敏化。目前,大多数生物分子疗法基于急性IVD变性模型,因此不能反映CD-LBP患者的真实临床慢性疼痛情况.未来的研究应旨在研究治疗性干预措施在包含已建立的感觉神经向内生长的慢性退化椎间盘中的作用。深入了解生物分子疗法对CD-LBP疼痛（慢性化）途径和疼痛缓解的影响，有助于缩小新型CD-LBP疗法的临床前工作台和临床床边之间的差距，并优化疼痛治疗。
