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Differences between tumor necrosis factor-alpha receptors types 1 and 2 in the modulation of spinal glial cell activation and mechanical allodynia in a rat sciatic nerve injury model.

Authors: Ishikawa, T  Miyagi, M  Kamoda, H  Orita, S  Eguchi, Y  Arai, G  Suzuki, M  Sakuma, Y  Oikawa, Y  Inoue, G  Aoki, Y  Toyone, T  Takahashi, K  Ohtori, S 
Citation: Ishikawa T, etal., Spine (Phila Pa 1976). 2013 Jan 1;38(1):11-6. doi: 10.1097/BRS.0b013e3182610fa9.
Pubmed: (View Article at PubMed) PMID:22652595
DOI: Full-text: DOI:10.1097/BRS.0b013e3182610fa9

STUDY DESIGN: 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)-alpha 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. SUMMARY OF BACKGROUND DATA: Recent research has revealed that activation of spinal glia plays an important role in radicular and neuropathic pain. TNF-alpha is reportedly a modulator for glial cell activation; however, the precise relationship between TNF-alpha 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. CONCLUSION: These results indicate that the microglial TNF-alpha p55 pathway played a more important role than the TNF-alpha p75 pathway in the pathogenesis of peripheral nerve injury pain. This suggests that future studies seeking to clarify neuropathic pain should target TNF-alpha and p55 receptors in microglia.


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RGD Object Information
RGD ID: 8661750
Created: 2014-06-13
Species: All species
Last Modified: 2014-06-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.