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
| Autor: | Sumihisa Orita, Masayuki Miyagi, Yasuhiro Oikawa, Yasuchika Aoki, Gen Inoue, Hiroto Kamoda, Yawara Eguchi, Seiji Ohtori, Miyako Suzuki, Kazuhisa Takahashi, Tomoaki Toyone, Yoshihiro Sakuma, Gen Arai, Tetsuhiro Ishikawa |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Internal medicine Neural Pathways medicine Animals Receptors Tumor Necrosis Factor Type II Orthopedics and Sports Medicine Microglia Glial fibrillary acidic protein biology business.industry Sciatic nerve injury medicine.disease Rats Disease Models Animal medicine.anatomical_structure Endocrinology Spinal Cord nervous system Hyperalgesia Receptors Tumor Necrosis Factor Type I Anesthesia Neuropathic pain Peripheral nerve injury biology.protein Neurology (clinical) Sciatic Neuropathy medicine.symptom Cell activation business Neuroglia Astrocyte |
| Zdroj: | Spine. 38:11-16 |
| ISSN: | 0362-2436 |
| DOI: | 10.1097/brs.0b013e3182610fa9 |
| Popis: | 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)-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. SUMMARY OF BACKGROUND DATA 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. CONCLUSION 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. |
| Databáze: | OpenAIRE |
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