Tumor necrosis factor-alpha levels correlate with postoperative pain severity in lumbar disc hernia patients: opposite clinical effects between tumor necrosis factor receptor 1 and 2

Lumbar disc hernia (LDH) is a leading cause of chronic pain in adults. The underlying pathology of chronic pain after discectomy remains unclear. Chronic local inflammation is considered to underlie painful symptomatology. In this context, we investigated tumor necrosis factor (TNF)-alpha, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2) expression at the time of surgery in LDH patients and correlated it with the severity of postoperative pain. We analyzed protein and mRNA levels from muscle, ligamentum flavum (LF), annulus fibrosus (AF), and nucleus pulposus (NP) in LDH patients and scoliosis patients (SP), who served as controls. Pain assessment with the visual analogue scale (VAS) was performed 1 day before surgery and 6 weeks and 12 months postoperatively. TNF-alpha protein levels were detected in AF, LF, and NP in all LDH patients, but not in SP. TNF-alpha mRNA was significantly greater in LDH patients than in SP; ie, 5-fold in AF, 3-fold in NP, and 2-fold in LF. For NP, TNF-alpha protein levels correlated with VAS scores (r=0.54 at 6-week and r=0.65 at 12-month follow-up). Also, TNFR1 protein levels in NP positively correlated with VAS scores (r=0.75 at 6-week and r=0.80 at 12-month follow-up). However, TNFR2 protein levels in AF negatively correlated with VAS scores (r=-0.60 at 6 weeks and r=-0.60 at 12 months follow-up). These data indicate that TNF-alpha levels could determine the clinical outcome in LDH patients after discectomy. Moreover, the opposite correlation of TNF receptors with pain sensation suggests that an unbalanced expression plays a role in the generation of pain.