Nerve tissue injury markers, inflammatory mechanisms and immunologic factors in lumbar disc herniation. Clinical and experimental studies

Abstract: The general concept for sciatic pain has for many decades been mechanical nerve root compression caused by a herniated disc. Recently evidence has indicated a more complex process, with a combination of mechanical and inflammatory/immunologic factors involved. The aim of these investigations was to analyze markers of nerve tissue injury, inflammation and immunologic factors in cerebrospinal fluid (CSF) and serum in patients with sciatica. Furthermore, the aim was to analyze the possible role of such inflammatory and immunologic factors in the pathophysiology of lumbar disc herniation and sciatica. The concentrations of four nerve tissue injury markers, neurofilament (NFL), S-100, glial fibrillary acidic protein (GFAp) and neuron specific enolase (NSE), were measured in CSF in patients with lumbar disc herniation and compared to control patients. The concentrations of NFL and S-100 were increased in CSF from patients with lumbar disc herniation, preferably in patients with short pain duration. In a disc herniation model in pig, changes in these nerve tissue injury markers, total protein and immunoglobulins were investigated in CSF. Nerve root compression was shown to induce an increase of NFL in CSF. Concentrations of five proinflammatory cytokines, IL-1b, IL-6, IL-8, IFN-g and TNF-a were assessed in CSF and serum from patients with disc herniation. The concentration of IL-8 was increased in CSF in 1/3 of the disc herniation patients, preferably in those with short pain duration. The involvement of nitric oxide (NO) in nucleus pulposus (NP) induced effects on spinal nerve roots were investigated in two animal models. Evidence was found for involvement of NO. The presence of auto-antibodies against glycosphingolipids was investigated in three groups of patients with sciatica. Increased serum titers of glycosphingolipid antibodies were found in approximately 2/3 of these patients. In summary, biomarkers of nerve root injury related to compression, inflammation and activation of the immune system can be detected in CSF and serum from patients with disc herniation, as well as in animal experimental models of disc herniation. Both inflammatory and immunologic mechanisms seem to be involved in the pathophysiology of sciatica caused by disc herniation.