Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Osteoarthritis Cartilage. 2021 Jan;29(1):17-27. doi: 10.1016/j.joca.2020.09.002. Epub 2020 Sep 30.
Low back pain (LBP) is a common musculoskeletal symptom, which can be developed in multiple clinical diseases. It is widely recognized that intervertebral disc (IVD) degeneration (IVDD) is one of the leading causes of LBP. However, the pathogenesis of IVD-related LBP is still controversial, and the treatment means are also insufficient to date. In recent decades, the role of structure and function changes of sensory nervous system in the induction and the maintenance of LBP is drawing more and more attention. With the progress of IVDD, IVD cell exhaustion and extracellular matrix degradation result in IVD structural damage, while neovascularization, innervation and inflammatory activation further deteriorate the microenvironment of IVD. New nerve ingrowth into degenerated IVD amplifies the impacts of IVD-derived nociceptive molecules on sensory endings. Moreover, IVDD is usually accompanied with disc herniation, which could injure and inflame affected nerves. Under mechanical and pro-inflammatory stimulation, the pain-transmitting pathway exhibits a sensitized function state and ultimately leads to LBP. Hence, relevant pathogenic factors, such as neurotrophins, ion channels, inflammatory factors, etc., are supposed to serve as promising therapeutic targets for LBP. The purpose of this review is to comprehensively summarize the current evidence on 1) the pathological changes of sensory nervous system during IVDD and their association with LBP, and 2) potential therapeutic strategies for LBP targeting relevant pathogenic factors.
下背痛（LBP）是一种常见的肌肉骨骼症状，可发生在多种临床疾病中。人们普遍认为椎间盘（IVD）退变（IVDD）是 LBP 的主要原因之一。然而，IVD 相关 LBP 的发病机制仍存在争议，且治疗手段也不足。近几十年来，感觉神经系统结构和功能变化在 LBP 的诱导和维持中的作用越来越受到关注。随着 IVDD 的进展，IVD 细胞耗竭和细胞外基质降解导致 IVD 结构损伤，而新生血管形成、神经支配和炎症激活进一步恶化 IVD 的微环境。新生神经长入退变的 IVD 会放大 IVD 来源的伤害性分子对感觉末梢的影响。此外，IVDD 通常伴有椎间盘突出，可损伤和炎症受累神经。在机械和促炎刺激下，疼痛传递通路表现出敏化功能状态，最终导致 LBP。因此，神经生长因子、离子通道、炎症因子等相关致病因子被认为是 LBP 的有前途的治疗靶点。本综述的目的是全面总结感觉神经系统在 IVDD 过程中的病理变化及其与 LBP 的关系，以及针对相关致病因子的 LBP 潜在治疗策略的现有证据。
