Cytokine Expression in the Epidural Space A Model of Noncompressive Disc Herniation-Induced Inflammation

Study Design. Animal study. Objective. Development of an animal model for the study of biochemical changes that occur in the epidural space after intervertebral disc herniation. Summary of Background Data. Although strong evidence for an inflammatory component exists, the biochemical processes underlying pain after disc herniation remain unknown. Methods. Epidural lavage was performed in 48 rats after L5 dorsal root ganglion exposure at baseline and 3, 6, or 24 hours after placement of autologous nucleus pulposus (NP) (N = 15), saline (N = 15), or NP + an interferon-gamma antibody (anti-IFN-gamma; N = 18) directly onto the dorsal root ganglion. Multiplex assays quantifying interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were performed. NP (N = 7) was also analyzed for these cytokines by placing NP into saline and measuring the relative concentration. Results. Cytokines measured low at baseline (0-100 pg/mL) in all groups. Compared with saline, NP application caused IL-6 elevation, peaking at T = 3 hours, that was prevented by anti-IFN-gamma. NP induced elevation of TNF-alpha, peaking at T = 24 hours and was prevented by anti-IFN-gamma. IFN-gamma was elevated after NP at T = 3 hours and T = 24 hours. IL-1 alpha was similar after saline versus NP. The concentrations of IL-1 beta and IL-10 were elevated at T = 3 hours, 6 hours, and 24 hours in all groups without between-groups difference. The level of IL-4 peaked at T = 3 hours in the NP group and was different than saline and NP + anti-IFN-gamma groups, but the time effect was insignificant. There was no change for GM-CSF. The concentration of cytokines measured in normal NP was less than 2 pg/mL for all cytokines except TNF-alpha. Conclusion. In this model of acute noncompressive disc herniation, NP caused the elevation of epidural IL-6, TNF-alpha, and IFN-gamma-all attenuated by IFN-gamma blockade. IL-1 beta and IL-10 were both significantly elevated by saline alone and their response was not prevented by IFN-gamma blockade. This model may prove useful for the study of the biochemical processes by which NP induces inflammation-induced nerve root irritation and radiculopathic pain.