##plugins.themes.bootstrap3.article.main##

##plugins.themes.bootstrap3.article.sidebar##

Published Dec 2, 2014

Fuzhou Wang  

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.

##plugins.themes.bootstrap3.article.details##

Keywords

Macrophage Migration Inhibitory Factor, Tumor Necrosis Factor, Spinal Cord, Inflammation, Neuropathic Pain

Supporting Agencies

This work was supported in part by the grants of the BASE Research Foundation (BASE2013002B), USA; National Natural Scientific Foundation of China (NSFC, 81271242 and 81371248); Nanjing Municipal Outstanding Young Scientist Grant, China (JQX12009) and Nanjing Municipal Youth Grants of Medical Science (QYK11139).

References
1. Walters ET. Neuroinflammatory contributions to pain after SCI: Roles for central glial mechanisms and nociceptor-mediated host defense. Exp Neurol 2014; 258C: 48-61.

2. Olmos G, Lladó J. Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014; 2014: 861231.

3. Granados-Soto V1, Alonso-López R, Asomoza-Espinosa R, Rufino MO, Gomes-Lopes LD, Ferreira SH. Participation of COX, IL-1 beta and TNF alpha in formalin-induced inflammatory pain. Proc West Pharmacol Soc 2001; 44: 15-17.

4. Kiguchi N, Maeda T, Kobayashi Y, Kishioka S. Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice. Neurosci Lett 2008; 445: 140-143.

5. Watkins LR, Goehler LE, Relton J, Brewer MT, Maier SF. Mechanisms of tumor necrosis factor-alpha (TNF-alpha) hyperalgesia. Brain Res 1995; 692: 244-250.

6. Onda A, Hamba M, Yabuki S, Kikuchi S. Exogenous tumor necrosis factor-alpha induces abnormal discharges in rat dorsal horn neurons. Spine 2002; 27: 1618-1624.

7. Hoi AY, Iskander MN, Morand EF. Macrophage migration inhibitory factor: a therapeutic target across inflammatory diseases. Inflamm. Allergy. Drug Targets 2007; 6: 183-190.

8. Wang F, Gao F, Jing L. Is macrophage migration inhibitory factor (MIF) the "control point" of vascular hypo-responsiveness in septic shock? Med Hypotheses 2005; 65: 1082-1087.

9. Rammos C, Hendgen-Cotta UB, Pohl J, Totzeck M, Luedike P, Schulze VT, Kelm M, Rassaf T. Modulation of circulating macrophage migration inhibitory factor in the elderly. Biomed Res Int 2014; 2014: 582586.

10. Vera PL, Wang X, Meyer-Siegler KL. Upregulation of macrophage migration inhibitory factor (MIF) and CD74, receptor for MIF, in rat bladder during persistent cyclophosphamide-induced inflammation. Exp Biol Med (Maywood) 2008; 233: 620-626.

11. Dickerhof N, Magon NJ, Tyndall JD, Kettle AJ, Hampton MB. Potent inhibition of macrophage migration inhibitory factor (MIF) by myeloperoxidase-dependent oxidation of epicatechins. Biochem J 2014; 462: 303-314.

12. Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J. Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats. Pain 2010;148: 275-283.

13. Wang F, Xu S, Shen X, Guo X, Peng Y, Yang J. Spinal macrophage migration inhibitory factor is a major contributor to rodent neuropathic pain-like hypersensitivity. Anesthesiology 2011; 114: 643-659.

14. Temple SE, Cheong KY, Price P, Waterer GW. Pathogenic bacteria and TNF do not induce production of macrophage migration inhibitory factor (MIF) by human monocytes. Cytokine 2009; 46: 316-318.

15. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994; 179: 1895-1902.

16. Xu S, Wu H, Wang X, Shen X, Guo X, Shen R, Wang F. Tumor suppressor menin mediates peripheral nerve injury-induced neuropathic pain through potentiating synaptic plasticity. Neuroscience 2012; 223: 473-485.

17. Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008; 28: 5189-5194.

18. Youn DH, Wang H, Jeong SJ. Exogenous tumor necrosis factor-alpha rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn. J Neurosci Res 2008; 86: 2867-2875.

19. Richards N, Batty T, Dilley A. CCL2 has similar excitatory effects to TNF-alpha in a subgroup of inflamed C-fiber axons. J Neurophysiol 2011; 106: 2838-2848.

20. Fehrenbacher JC, Burkey TH, Nicol GD, Vasko MR. Tumor necrosis factor alpha and interleukin-1beta stimulate the expression of cyclooxygenase II but do not alter prostaglandin E2 receptor mRNA levels in cultured dorsal root ganglia cells. Pain 2005; 113:113-122.

21. Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 2005; 25: 3219-3228.

22. Cvetkovic I, Stosic-Grujicic S: Neutralization of macrophage migration inhibitory factor-novel approach for the treatment of immunoinflammatory disorders. Int Immunopharmacol 2006; 6: 1527-1534.

23. Kasama T, Ohtsuka K, Sato M, Takahashi R, Wakabayashi K, Kobayashi K. Macrophage migration inhibitory factor: a multifunctional cytokine in rheumatic diseases. Arthritis 2010; 2010: 106202.

24. Timlin H, Bingham CO III. Efficacy and safety implications of molecular constructs of biological agents for rheumatoid arthritis. Expert Opin Biol Ther 2014; 14: 893-904.

25. Hanauer SB. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: overview of randomized clinical studies. Rev Gastroenterol Disord 2004; 4(Suppl 3): S18-S24.

26. Hwang YG, Moreland LW. Induction therapy with combination TNF inhibitor and methotrexate in early rheumatoid arthritis. Curr Rheumatol Rep 2014; 16: 417.

27. Singh A, Leng L, Fan J, Gajda M, Bräuer R, Fingerle-Rowson G, Bucala R, Illges H: Macrophage-derived, macrophage migration inhibitory factor (MIF) is necessary to induce disease in the K/BxN serum-induced model of arthritis. Rheumatol Int 2013; 33: 2301-2308.

28. Wijbrandts CA, van Leuven SI, Boom HD, Gerlag DM, Stroes EG, Kastelein JJ, Tak PP. Sustained changes in lipid profile and macrophage migration inhibitory factor (MIF) levels after anti-TNF therapy in rheumatoid arthritis. Ann Rheum Dis 2009; 68:1316-1321.

29. Miyauchi T, Tsuruta R, Fujita M, Kaneko T, Kasaoka S, Maekawa T. Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study. BMC Infect Dis 2009; 9:209.
How to Cite
Wang, F. (2014). Pathological Contribution of Spinal Macrophage Migration Inhibitory Factor to Neuropathic Hypersensitivity through Interacting with TNF-alpha in the Rat. Science Insights, 10(2-3), 283–290. https://doi.org/10.15354/si.14.ar109
Section
Original Article