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

摘要

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.