Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice.
METHODS
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-alpha in the nucleus pulposus (NP) on nerve roots.


BACKGROUND
Radicular pain is induced by mechanical compression and inflammation of nerve roots. Many authors have reported that following disc herniation, producing TNF-alpha plays a major role in neuropathic pain. Their findings suggest that TNF-alpha 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.


CONCLUSIONS
In this study TNF-alpha 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-alpha in the NP appears to mediate pain, but not cause an increase in CGRP in the DRG neurons.
Yamashita
Masaomi
M
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. masaomiym@aol.com
Ohtori
Seiji
S
Koshi
Takana
T
Inoue
Gen
G
Yamauchi
Kazuyo
K
Suzuki
Munetaka
M
Takahashi
Kazuhisa
K
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D007403:Intervertebral Disc / Q000502:physiology*; D007405:Intervertebral Disc Displacement / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D011843:Radiculopathy / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018836:Inflammation Mediators; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha; D015740:Calcitonin Gene-Related Peptide