Introduction: The painful clinical sequelae associated with sciatica secondary to intervertebral disc herniation have been traditionally attributed to mechanical compression of the spinal nerve root. More recent studies have also implicated inflammatory mediators and microvascular changes in the pathogenesis of acute sciatica. The application of nucleus pulposus (NP) to a spinal nerve root has been shown to induce thrombus formation in the associated nerve microvasculature and result in greater injury to the axons in the centre then in the periphery, suggesting an ischemic mechanism of injury. The spinal nerve blood flow changes that are associated with nerve dysfunction seen in acute sciatica, offer a potential target for therapeutic intervention. The VEGF angiogenic cytokines have been demonstrated to be potent stimulators of the differentiation and function of vascular endothelial cells after injury. The goal of this study was to determine the relationship between the severity of spinal nerve root injury in patients with acute sciatica secondary to lumbar disc herniation (AS/LDH) undergoing surgical discectomy and the levels of VEGF-A and VEGF-B in serum, spinal nerve root lavage and disc tissue homogenate.
Methods: 24 patients with AS/LDH of less than 16 weeks duration, undergoing laminectomy discectomy surgery were included in this study. At the time of surgery, the spinal nerve root was lavaged with 5 cc of saline, the extruded disc tissue removed surgically and serum samples were obtained. Disc and lavagate samples were stored in physiological buffer with protease inhibitors at -80°C. The concentrations (pg/ml) of VEGF-A and VEGF-B and the inflammatory cytokines TNFα, and IL-2, 6 and 8 inflammatory in disc herniated nucleus pulposus tissue homogenate (HNP-H), spinal nerve root lavagate (SN-L) and in serum were measured in triplicate using ELISA cytokine immunoassay. Research ethics committee approval was obtained.
Results: In AS/LDH patients, VAS leg pain scores and significant spinal nerve root motor weakness scores (3.0 - 4.0/5) correlated closely with serum and HNP-H tissue levels of VEGF-A and VEGF-B (Pearson r = 0.78). In 11/24 patients, elevated VEGF-A and B concentrations correlated to a moderate degree with TNFα and IL-2, 6 and 8 inflammatory cytokine levels (r = 0.61). Low concentrations of VEGF and inflammatory cytokine concentrations were seen in all SN-L test samples.
Discussion: These findings provide preliminary evidence that the severity of spinal nerve root injury in patients with acute sciatica secondary to lumbar disc herniation, is related to a combined mechanism, involving ischemic and inflammatory components. In addition to a possible future avenue for targeted therapeutic intervention, the correlation of elevated serum concentrations of VEG angiogenic cytokines with the severity of spinal nerve root injury in this patient population may be an important diagnostic biomarker in clinical decision making.
This research study was funded by grants from the National Institutes of Health, Bethesda, USA and from the University of British Columbia Orthopaedic Research Excellence Fund.