Introduction: Vertebral endplate defects are often implicated in lumbar degenerative diseases, yet their connection to patient-reported symptoms remains unclear. COX-2 and PGE-2 are known for their roles in inflammation and pain, with EP-4 receptor involvement in pain signaling. Examining their expression in vertebral endplate tissues may provide insights into pathomechanism of low back pain. This study aimed to investigate the associations between endplate defects and patient-reported symptoms and to further clarify the role of COX-2/PGE-2/EP-4 axis in the pathogenesis of chronic low back pain.
Methods: A total of 71 patients were included in this study, including 18 patients diagnosed with lumbar disc herniation, 19 with lumbar disc herniation accompanied by degenerative lumbar spinal stenosis, and 34 with degenerative spondylolisthesis. Demographic data, Pfirrmann grade, Modic changes, endplate defect score, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI) before surgery, 3-month and 6-month follow up, and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. Patients were divided into Defect and Non-defect groups according to endplate morphology on lumbar MR. All intraoperative endplate specimens were immediately fixed in 10% formaldehyde, then embedded in paraffin 3 days later for tissue sections. The outcome measures were compared between the Defect group and Non-defect group.
Results: The age of Defect group was significantly higher than that of Non-defect group (52.5±7.7 vs. 57.2±9.1. P=0.024). There were no significant differences in gender, diagnosis, or BMI between the two groups. Modic changes (Type Ⅱ/Type Ⅲ) were more common in patients of Defect group than Non-defect group (38.5% vs. 11.1%, P＜0.001), and so was disc degeneration (Pfirrmann grade Ⅳ/Ⅴ) (69.2% vs. 33.3%, P＜0.001). Defect group had significantly higher VAS-Back (6.5±2.0 vs. 4.9±1.6, P<0.001) and ODI scores (62.9±10.7 vs. 45.2±14.8, P<0.001) than Non-defect group, while there was no significant differences between the two groups during the 3 and 6-month follow-up after surgery. Histologically, Defect group was characterized with upregulation of COX-2, PGE-2, and EP-4 in endplate tissue sections. Both in Defect and Non-defect group, VAS-Back showed moderate positive correlations with the expressions of COX-2 (r=0.643; r=0.558, p both＜0.001), PGE-2 (r=0.611; r=0.640, p both＜0.001), and EP-4 (r=0.643; r=0.563, p both＜0.001). Multivariate regression analyses reveled that percentage of COX-2-positive cells was associated with endplate defects (OR=1.509, 95%CI [1.048~2.171], P=0.027), as well as percentage of PGE-2-positive (OR=1.291, 95%CI [1.106~1.508], P=0.001) and EP-4-positive cells (OR=1.284, 95%CI [1.048~2.171], P=0.003).
Discussion: The present study compared patient-reported symptoms between Defect and Non-defect group, assessed the expression levels of COX-2/PGE-2/EP-4 axis in endplate tissue sections, and analyzed their associations. Our results revealed that patients with endplate defects experienced poorer quality of life. Moreover, a significant correlation was observed between patient-reported symptoms and the percentage of immune-positive cells (COX-2, PGE-2, and EP-4) in endplate tissue sections. A higher expression of COX-2/PGE-2/EP-4 axis may be a risk factor for the development of endplate defects. These inflammatory factors could significantly influence the pathophysiology of endplate defects and might serve as crucial targets for improving patients' quality of life.