Pathological Contribution of Spinal Macrophage Migration Inhibitory Factor to Neuropathic Hypersensitivity through Interacting with TNF-alpha in the Rat
Journal Title: Science Insights - Year 2014, Vol 10, Issue 2
Abstract
BACKGROUND Our previous data demonstrated that the proinflammatory cytokine macrophage migration inhibitory factor (MIF), a pleiotropic cytokine produced mainly by nonneuronal tissue, has been implicated in the pathogenesis of inflammatory and neuropathic hypersensitivity, whereas the precise underlying mechanisms are not totally elucidated. The aim of this study was to examine the interacting role for spinal MIF with TNF-alpha in neuropathic pain. METHODS After approval by the institutional Animal Care and Use Committee, the randomized Sprague-Dawley rats underwent prophylactic intrathecal administration of recombinant MIF (rMIF), TNF-alpha, MIF mAb, TNF-alpha mAb, or in combination prior to the spared nerve injury (SNI). Thermal hyperalgesia with hot plate and tactile allodynia using von Frey filaments were assessed after different interventions. Spinal cord levels of MIF and TNF-alpha were measured using Western Blotting and immunocytochemistry. RESULTS Exogenous rMIF potentiated SNI-induced nociceptive behavior that were not evoked by single use of rMIF without SNI, and this potential effect could be blocked by MIF antibody in part. After giving rMIF combined with TNF-alpha to SNI animals, the perception of thermal and tactile stimuli was maximized. Spinal MIF mAb inhibited TNF-alpha expression, and vise versa for TNF-alpha Ab on MIF expression after SNI. rMIF or TNF-alpha combined to SNI produced more significant effect on the levels of MIF and TNF-alpha than SNI alone, and this effect could be furthered by administering rMIF and TNF-alpha together. CONCLUSION These data demonstrate that proinflammatory cytokine MIF is involved in the peripheral nerve injury-induced hypersensitivity through potentiating spinal TNF-alpha signaling.
Authors and Affiliations
Fuzhou Wang
Keywords
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- EP ID EP689577
- DOI 10.15354/si.14.ar109
- Views 179
- Downloads 0
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