Differences between tumor necrosis factor-α receptors types 1 and 2 in the modulation of spinal glial cell activation and mechanical allodynia in a rat sciatic nerve injury model.
METHODS
Immunohistological analysis of spinal glial cells and analysis of pain behavior in the rat neuropathic pain model were investigated to clarify the function of tumor necrosis factor (TNF)-α receptors p55 type 1 and p75 type 2.


OBJECTIVE
Our objective was to investigate changes in hyperalgesia and glial cell activation after injection of antibodies to each TNF receptor in a rat sciatic nerve injury model.


BACKGROUND
Recent research has revealed that activation of spinal glia plays an important role in radicular and neuropathic pain. TNF-α is reportedly a modulator for glial cell activation; however, the precise relationship between TNF-α and its 2 receptors on glial cells has not been fully delineated.


METHODS
Chronic constriction sciatic nerve injury and sham-operated rats were used. Antibodies to p55 or p75 or saline were intrathecally injected at the L5 level into rats with chronic constriction injury. Mechanical allodynia was examined for 2 weeks. Spinal cords were removed for immunohistochemical studies of ionized calcium-binding adaptor molecule 1 or glial fibrillary acidic protein.


RESULTS
Saline rats showed significantly more mechanical allodynia and the number of ionized calcium-binding adaptor molecule 1--immunoreactive microglia and glial fibrillary acidic protein--immunoreactive astrocytes were significantly increased in the saline rats compared with sham-operated rats during the 2 weeks. Injection of both antibodies significantly reduced pain behavior and anti-p55 caused significantly greater reduction compared with anti-p75. The numbers of microglia in both the antibodies groups were significantly decreased when compared with the saline group. In addition, the anti-p55 antibody suppressed microglial activation more than the anti-p75 antibody.


CONCLUSIONS
These results indicate that the microglial TNF-α p55 pathway played a more important role than the TNF-α p75 pathway in the pathogenesis of peripheral nerve injury pain. This suggests that future studies seeking to clarify neuropathic pain should target TNF-α and p55 receptors in microglia.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. ishikawa_tetsuhiro@yahoo.co.jp
Tetsuhiro
T
Ishikawa
Masayuki
M
Miyagi
Hiroto
H
Kamoda
Sumihisa
S
Orita
Yawara
Y
Eguchi
Gen
G
Arai
Miyako
M
Suzuki
Yoshihiro
Y
Sakuma
Yasuhiro
Y
Oikawa
Gen
G
Inoue
Yasuchika
Y
Aoki
Tomoaki
T
Toyone
Kazuhisa
K
Takahashi
Seiji
S
Ohtori
D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology; D009434:Neural Pathways / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506237:Tnfrsf1a protein, rat