年轻成年人的慢性下腰痛:神经炎症与退变的病理生理方面

Chronic Low Back Pain in Young Adults: Pathophysiological Aspects of Neuroinflammation and Degeneration.

作者信息

Pravdyuk Natalya G, Buianova Anastasiia A, Novikova Anna V, Klimenko Alesya A, Ignatyuk Mikhail A, Malykhina Liubov A, Patsap Olga I, Atiakshin Dmitrii A, Timofeev Vitaliy T, Shostak Nadezhda A

机构信息

Acad. A. I. Nesterov Department of Faculty Therapy, Pirogov Russian National Research Medical University, 1, Ostrovityanova St., 117997 Moscow, Russia.

Research and Educational Resource Centre for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Patrice Lumumba Peoples' Friendship University of Russia (RUDN University), 6, Miklukho-Maklaya St., 117198 Moscow, Russia.

出版信息

Int J Mol Sci. 2025 Aug 6;26(15):7592. doi: 10.3390/ijms26157592.

Abstract

Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive's criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10-12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, = 0.031). NGF expression was significantly elevated in degenerated discs ( = 0.0287) and strongly correlated with SP (r = 0.785, = 5.268 × 10). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP.

摘要

椎间盘退变疾病(DDD)是慢性下腰痛(LBP)的主要原因,但驱动椎间盘退变和疼痛的分子机制仍知之甚少。本研究分析了36例患有椎间盘突出症和下腰痛的年轻患者(中位年龄 = 36.00 [31.00, 42.50]岁)的椎间盘组织,并与健康对照进行比较,以研究细胞外基质(ECM)的变化和神经化学改变。使用MRI(Pfirrmann分级)和组织学(Sive标准)评估椎间盘退变。采用组织化学和免疫组织化学方法评估聚集蛋白聚糖含量、钙化以及神经生长因子(NGF)、P物质(SP)和S-100蛋白的表达。MRI结果包括Pfirrmann V级(30.55%)、IV级(61.11%)、III级(5.56%)和II级(2.78%)。3例患者观察到严重的组织学退变(10 - 12分)。聚集蛋白聚糖减少与疼痛持续时间延长相关(r = 0.449,P = 0.031)。退变椎间盘中NGF表达显著升高(P = 0.0287),且与SP密切相关(r = 0.785,P = 5.268×10)。5例患者中发现游离神经末梢。36.1%的患者存在ECM钙化,与神经根病显著相关(r = 0.664,P = 0.005)。观察到的NGF和SP共定位表明它们在疼痛发生中起协同作用。这些结果表明,在年轻人中,聚集蛋白聚糖丢失、神经化学失衡和ECM钙化是DDD和慢性LBP的关键因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539d/12347870/a7831a6c3b6c/ijms-26-07592-g001.jpg

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