Study Design.
Changes in behavior and the immunohistochemistry of dorsal root ganglion (DRG) neurons were examined using a mouse model of radicular pain.
Objective.
To examine the effects of TNF-α in the nucleus pulposus (NP) on nerve roots.
Summary of Background Data.
Radicular pain is induced by mechanical compression and inflammation of nerve roots. Many authors have reported that following disc herniation, producing TNF-α plays a major role in neuropathic pain. Their findings suggest that TNF-α contained in the NP is significant in the development of pain and nerve root degeneration, but it has not been clearly demonstrated.
Methods.
Wild-type NPs or TNF-KO NPs, which were harvested from C57BL/6 mice (wild-type NP) or TNF-knock-out mice (TNF-KO NP), were applied to the left sciatic nerves of 30 wild-type mice, and the nerves were pinched. Production of hind paw mechanical allodynia, activating transcription factor 3, and calcitonin gene- related peptide (CGRP) were assessed.
Results.
Animals receiving a NP application demonstrated significant mechanical allodynia compared to the pinch-only and the control groups. The degree of mechanical allodynia was greater in the wild-type than in the TNF-KO group. The number of activating transcription factor 3 immunoreactive neurons was significantly higher in the wild-type than in the TNF-KO group. The number of CGRP-immunoreactive neurons was higher in the wild-type and TNF-KO than in the control groups. However, no significant difference in activity was observed between both CGRP positive groups.
Conclusion.
In this study TNF-α contained in the NP was important for the production of radicular pain accompanied by long-lasting degeneration of DRG neurons. However, other cytokines in the NP and nerve compression may also play important roles in pain transmission. In this model system, TNF-α in the NP appears to mediate pain, but not cause an increase in CGRP in the DRG neurons.
