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THE ROLE OF TUMOR NECROSIS FACTOR A (TNFα) AND NITRIC OXIDE SYNTHASE IN SCIATIC PAIN (AN EXPERIMENTAL HUMAN STUDY)



Abstract

Study design: An experimental human study of retrieval material.

Objectives: Assessment and evaluation of the involvement of TNFα and Nitric oxide in sciatic pain.

Summary and background data: It appears that the inflammation produced by the herniated fragment is at least partially related to the sciatic pain. TNFα was found to be expressed by herniated nucleus polposus of rats and exogenous TNFα applied in vivo to rat nerve root produced neuropathologic changes and behavior deficit that mimicked experimental studies with herniated nucleus polposus (HNP) applied to nerve roots. Nitric oxide was shown to be involved in the mechanism that produce mechanical and thermal hyperalgesia in rats. Nitric oxide synthesis can be induced by different cytokines among them TNFα and is mediated by the enzyme Nitric oxide synthase. The current study was performed in order to evaluate the possible mechanism of action of TNFα in human herniated discs and define the relationship between nitric oxide and TNFα production by human discs.

Methods: Six herniated fragments of lumbar discs were compared to a similar number of normal intervertebral discs removed during spinal fusion procedures of the lumbar and thoracic spine for the presence of TNFα and the expression of Nitric oxide synthase.

Results: TNFα was expressed by chondrocytes of the herniated fragments but not by the same cells in normal discs. Similar expression pattern was noted for nitric oxide synthase. Both materials were not expressed in the healthy discs.

Conclusions: TNFα appears to be related to pain mechanism of disc herniation. It’s effect is mediated through Nitric oxide. It is well known that NSAIDs are relatively inefficient in modulating TNF-related pain. This might explain the lack of efficacy of currently used medications.

The abstracts were prepared by Orah Naor. Correspondence should be addressed to him at the Israel Orthopaedic Association, PO Box 7845, Haifa 31074, Israel.