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Wnt Signaling in the Pathogenesis of Multiple Sclerosis-Associated Chronic Pain

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Abstract

Many multiple sclerosis (MS) patients develop chronic pain, but the underlying pathological mechanism is unknown. Mice with experimental autoimmune encephalomyelitis (EAE) have been widely used to model MS-related neurological complications, including CNS demyelination, neuroinflammation and motor impairments. Similar to MS patients, EAE mice also develop chronic pain. We are interested in elucidating the potential involvement of Wnt signaling in the pathogenesis of chronic pain in EAE mice. In this study, we characterized the expression of Wnt signaling proteins in the spinal cord dorsal horn (SCDH) of EAE mice, by immunoblotting and immunostaining. The EAE model was created by immunization of adult mice (C57BL/6, 10 weeks) with myelin oligodendrocyte glycoprotein (MOG) 35–55. Robust mechanical hyperalgesia and allodynia were developed in both fore- and hindpaws of the EAE mice. Wnt3a, a prototypical Wnt ligand for the canonical pathway, was significantly increased in the SCDH of the EAE mice. Another key protein in the canonical pathway, ß-catenin, was also significantly up-regulated. In addition, Wnt5a, a prototypic Wnt ligand for the non-canonical pathway, and its receptor (co-receptor) Ror2 were also up-regulated in the SCDH of the EAE mice. We further found that Wnt5a antagonist Box5 and β-catenin inhibitor indomethacin attenuated mechanical allodynia in the EAE mice. Our data collectively suggest that Wnt signaling pathways are up-regulated in the SCDH of the EAE mice and that aberrant activation of Wnt signaling contributes to the development of EAE-related chronic pain.

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Acknowledgments

This work was supported by the UTMB start-up funds and the Tuberous Sclerosis Alliance to S.-J. T., the National Natural Science Foundation of China (No. 30873457 to L. Z. and the Scientific Technology Project of Guangdong Province of China (No.2008A060202010 and No. 2010B050700019 to L. Z.).

Conflict of Interest Disclaimer

The authors claim that this data set is original and is not under consideration elsewhere. All authors have approved the final version of the manuscript and have no financial or other relationship that might lead to a conflict of interest.

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  1. Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX, 77555, USA

    Subo Yuan, Yuqiang Shi & Shao-Jun Tang

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  1. Subo Yuan
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  2. Yuqiang Shi
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Correspondence to Shao-Jun Tang.

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Yuan, S., Shi, Y. & Tang, SJ. Wnt Signaling in the Pathogenesis of Multiple Sclerosis-Associated Chronic Pain. J Neuroimmune Pharmacol 7, 904–913 (2012). https://doi.org/10.1007/s11481-012-9370-3

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