Local application of disc-related cytokines on spinal nerve roots

Study Design. To analyze the effects of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma on,cauda equina function and to define if any of these cytokines could induce nerve root dysfunction comparable with the situation-with application of nucleus pulposus. Summary of Background Data. Proinflammatory cytokines derived from the intervertebral disc have been suggested to mediate the nucleus pulposus-induced nerve root injury following local application of nucleus pulposus. However, it is not known if such cytokines may induce similar injury if applied separately. Methods. A total of 29 pigs were used. Nucleus pulposus was harvested from lumbar discs and applied to the-sacrococcygeal cauda equina following laminectomy of the first coccygeal vertebra in seven pigs. Five pigs received 1.6 mug of tumor necrosis factor-alpha, five pigs received 0.85 mug of interleukin-1beta, and five pigs received 1.66 mug of interferon-gamma. Seven pigs received autologous fat for control. Nerve conduction velocity was studied by local electrical stimulation and recordings in the tail muscles 7 days after the application. Results. Application of nucleus pulposus and fat induced similar effects as seen in previous studies, with normal nerve conduction velocity for fat and a significant reduction for nucleus pulposus. Application of both interleukin-1beta and IFN-gamma induced slight reductions of nerve conduction velocity compared with fat, but they were not statistically; significant. Tumor necrosis factor-alpha, however, induced a reduction of the velocity that was even more pronounced than for nucleus pulposus. Conclusion. Based on previous observations and the data of the present study, one may conclude that tumor necrosis factor-alpha from nucleus pulposus cells seems to be intimately involved with the basic pathophysiologic events leading to both nerve toot dysfunction and pain after local, epidural application of nucleus pulposus. One may therefore also suspect that pharmacologic inhibition of tumor necrosis factor-alpha may at least theoretically be considered in the clinical situation with disc herniation and sciatica.