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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 83–91, January 2013
How to Cite
Tao, F., Li, Q., Liu, S., Wu, H., Skinner, J., Hurtado, A., Belegu, V., Furmanski, O., Yang, Y., McDonald, J. W. and Johns, R. A. (2013), Role of Neuregulin-1/ErbB Signaling in Stem Cell Therapy for Spinal Cord Injury-Induced Chronic Neuropathic Pain. STEM CELLS, 31: 83–91. doi: 10.1002/stem.1258
Author contributions: F.T., Q.L., and S.L.: conception and design, collection and analysis of data, and manuscript writing; H.W. and J.S.: collection of data; A.H., V.B., O.F., and Y.Y.: administrative support; J.W.M. and R.A.J.: conception and design and financial support. F.T., Q.L., and S.L. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 23, 2012.
- Issue online: 19 DEC 2012
- Version of Record online: 19 DEC 2012
- Accepted manuscript online: 23 OCT 2012 06:43AM EST
- Manuscript Accepted: 1 OCT 2012
- Manuscript Received: 16 JUL 2012
- Maryland Stem Cell Research Fund. Grant Number: 2009-MSCRFII-0014-00
- Spinal cord injury;
- Chronic neuropathic pain;
- Stem cell transplantation;
- Neuregulin-1/ErbB signaling
Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination in the injured spinal cord and reduces SCI-induced chronic neuropathic pain. Moreover, we found that SCI reduces the protein level of neuregulin-1 and ErbB4 in the injured spinal cord and that OPC transplantation enhances the spinal expression of both proteins after SCI. Finally, intrathecal injection of neuregulin-1 small interfering RNA, but not the control nontarget RNA, diminishes OPC transplantation-produced remyelination and reverses the antinociceptive effect of OPC transplantation. Our findings suggest that the transplantation of embryonic stem cell-derived OPCs is an appropriate therapeutic intervention for treatment of SCI-induced chronic neuropathic pain, and that neuregulin-1/ErbB signaling plays an important role in central remyelination under pathological conditions and contributes to the alleviation of such pain. STEM Cells2013;31:83–91