Tumor Necrosis Factor α and Nucleus-Pulposus-Induced Nerve Root Injury

Abstract

STUDY DESIGN: The effects of nucleus pulposus and various treatments to block tumor necrosis factor alpha activity were evaluated in an experimental set-up using immunohistochemistry and nerve conduction velocity recordings. OBJECTIVES: To assess the presence of tumor necrosis factor alpha in pig nucleus pulposus cells, and to see if block of tumor necrosis factor alpha also blocks the nucleus-pulposus-induced reduction of nerve root conduction velocity. SUMMARY AND BACKGROUND DATA: A meta-analysis of observed effects induced by nucleus pulposus revealed that these effects might relate to one specific cytokine-tumor necrosis factor alpha. METHODS: Series-1: Cultured nucleus pulposus cells were stained immunohistologically with a monoclonal antibody for tumor necrosis factor alpha. Series-2: Nucleus pulposus was harvested from lumbar discs and applied to the sacrococcygeal cauda equina in 13 pigs autologously. Four pigs received 100 mg of doxycycline intravenously; five pigs had a blocking monoclonal antibody to tumor necrosis factor alpha applied locally in the nucleus pulposus, and four pigs remained nontreated, forming a control group. Three days after the application, the nerve root conduction velocity was determined over the application zone by local electrical stimulation. RESULTS: Series-1: Tumor necrosis factor alpha was found to be present in the nucleus pulposus cells. Series-2: The selective antibody to tumor necrosis factor alpha limited the reduction of nerve conduction velocity, although in comparison with the control group this was not statistically significant. However, treatment with doxycycline significantly blocked the nucleus-pulposus-induced reduction of conduction velocity. CONCLUSION: For the first time, a specific substance, tumor necrosis factor alpha, has been linked to the nucleus-pulposus-induced effects of nerve roots after local application. Although the effects of this substance may be synergistic with those of other similar substances, the data of the current study may be of significant importance for the continued understanding of nucleus pulposus' biologic activity, and of possible potential use for future strategies in managing sciatica.