Introduction Degenerative disc disease (DDD) is a major cause of lower back pain (LBP). Key pathological processes of intervertebral disc (IVD) degeneration include extracellular matrix (ECM) degradation (including aggrecan loss), cartilage dehydration, and pathological ingrowth of blood vessels and nerve fibers. Neurotrophins and neuropeptides, such as nerve growth factor (NGF) and substance P (SP), play an essential role in LBP pathogenesis, neoinnervation, inflammation, and the maintenance of chronic pain.

Materials and Methods Thirty-six young patients (mean age 36.00 [31.00, 42.50] years) with LBP associated with herniated discs and five healthy individuals were enrolled. IVD samples were collected during microdiscectomy. MRI-based Pfirrmann classification (2001) was used to assess the stages of disc degeneration. Histological grading was performed according to Sive’s criteria (2002). Histochemical staining (hematoxylin-eosin, Alizarin Red, Safranin O/Fast Green FCF) was conducted to evaluate ECM status, including aggrecan content. Immunohistochemical analysis was performed to assess NGF, S-100 protein, and SP expression.

Results All patients experienced chronic LBP. According to MRI, Pfirrmann grade V degeneration was found in 30.55% of patients, grade IV in 61.11%, grade III in 5.56%, and grade II in 2.78%. Histologically confirmed degeneration was observed in 23 cases (63.88%), with 3 patients showing severe degeneration (10-12 points). In patients with longer pain episodes (average duration 11.29 weeks), aggrecan loss was observed in 19.4% of cases (r=0.449; P=0.031). NGF expression was significantly higher in degenerated discs (P=0.0287) and positively correlated with SP levels (r=0.785; P=5.268 × 10−9). Increased NGF and SP expression were noted in patients with osteophytes, with levels correlating with both the histological degeneration score and MRI grading. Isolated free nerve endings were detected in the nucleus pulposus of 5 patients. Calcification was observed in 36.1% of cases, predominantly around hypertrophic chondrocytes and their clusters, and its severity correlated with radiculopathy (r=0.664; P=0.005).

Conclusion In young individuals, aggrecan loss, increased expression of NGF, SP, S-100 protein, and ECM calcification are key pathological features of IVD degeneration contributing to chronic LBP. The colocalization of NGF and SP suggests a synergistic role in the development of chronic pain. These findings highlight new therapeutic targets aimed at inhibiting pathological neoinnervation and ECM degradation.

The authors have declared no competing interest.

This research was carried out within the state assignment for Acad. A. I. Nesterov Department of Faculty Therapy, Pirogov Russian National Research Medical University (#04200729490).

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The Ethics Committee of Pirogov Russian National Research Medical University gave ethical approval for this work (protocol No. 208 dated 17 May 2021).

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