Cardenas Ashley, Fidai Alikhan B, Ikwuegbuenyi Chibuikem A, Robayo Anthony, Willett Noah, Hussain Ibrahim, Härtl Roger, Bonassar Lawrence J
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Department of Neurological Surgery, Och Spine at New York Presbyterian Hospital, Weill Cornell Medicine, New York, New York, USA.
World Neurosurg. 2025 Aug;200:124122. doi: 10.1016/j.wneu.2025.124122. Epub 2025 Jun 2.
Intervertebral disc (IVD) degeneration is a common source of back pain. The IVD is a complex structure that consists of an outer annular ring, an inner nucleus pulposus, and flanking cartilaginous endplates, which together allow for daily mobility by distributing loads and acting as a flexible segment within the spine. Both age and mechanical overload can drive the development of a pathologic disc microenvironment that includes alterations in mechanics, solute transport, and inflammation. Such changes in the disc have negative consequences on resident cells that promote their senescence, apoptosis, and contribution to furthering disc degeneration through mitochondrial dysfunction and the release of reactive oxygen species, proteases, and cytokines. This crosstalk between IVD cells and their microenvironment creates a feedback loop that eventually manifests into such clinical conditions as disc height loss, herniations, and total IVD collapse. Developing a holistic understanding of how this feedback loop is initiated and may be halted will enable the development of novel therapeutics that not only provide analgesic benefit but also help rebuild the deteriorated disc.
椎间盘退变是背痛的常见原因。椎间盘是一种复杂的结构，由外层纤维环、内层髓核和两侧的软骨终板组成，它们共同通过分散负荷并作为脊柱内的一个灵活节段来实现日常活动。年龄和机械过载均可促使病理性椎间盘微环境的形成，其中包括力学、溶质转运和炎症的改变。椎间盘中的这些变化会对驻留细胞产生负面影响，促使其衰老、凋亡，并通过线粒体功能障碍以及活性氧、蛋白酶和细胞因子的释放，进一步推动椎间盘退变。椎间盘细胞与其微环境之间的这种相互作用形成了一个反馈回路，最终表现为椎间盘高度降低、突出和椎间盘完全塌陷等临床病症。全面了解这个反馈回路是如何启动以及如何可能被阻断，将有助于开发新的治疗方法，这些方法不仅能提供止痛效果，还能帮助修复退变的椎间盘。
