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Translational and Clinical Research
Version of Record online: 26 JUL 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 8, pages 1294–1303, August 2011
How to Cite
Guo, W., Wang, H., Zou, S., Gu, M., Watanabe, M., Wei, F., Dubner, R., Huang, G. T.-J. and Ren, K. (2011), Bone Marrow Stromal Cells Produce Long-Term Pain Relief in Rat Models of Persistent Pain. STEM CELLS, 29: 1294–1303. doi: 10.1002/stem.667
Author contributions: W.G.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; H.W., S.Z., and M.W.: collection and assembly of data; M.G.: conception and design, collection and assembly of data, data analysis and interpretation; F.W.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, financial support; R.D.: conception and design, data analysis and interpretation, manuscript writing, financial support, final approval of manuscript; G.T.-J. H.: conception and design, data interpretation, manuscript writing, financial support, final approval of manuscript; K.R.: conception and design, assembly of data, data analysis and interpretation, manuscript writing, financial support; final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS May 31, 2011.
- Issue online: 26 JUL 2011
- Version of Record online: 26 JUL 2011
- Accepted manuscript online: 31 MAY 2011 03:09PM EST
- Manuscript Accepted: 13 MAY 2011
- Manuscript Received: 24 FEB 2011
- NIH. Grant Numbers: DE11964, DE018573, NS060735, NS059028, DE019156
- Grant-in-Aid for Scientific Research. Grant Number: 22592039
- Japanese Ministry of Education, Science and Culture
- Adult stem cells;
- Bone marrow stromal cells;
- Cellular therapy;
- Rat model;
- Stem cell transplantation
Chronic pain conditions are difficult to treat and are major health problems. Bone marrow stromal cells (BMSCs) have generated considerable interest as a candidate for cell-based therapy. BMSCs are readily accessible and are easy to isolate and expand ex vivo. Clinical studies show that direct injection of BMSCs does not produce unwanted side effects and is well tolerated and safe. Here, we show that a single systemic (intravenous) or local injection (into the lesion site) of rat primary BMSCs reversed pain hypersensitivity in rats after injury and that the effect lasted until the conclusion of the study at 22 weeks. The pain hypersensitivity was rekindled by naloxone hydrochloride, an opioid receptor antagonist that acts peripherally and centrally, when tested at 1–5 weeks after BMSC infusion. In contrast, naloxone methiodide, a peripherally acting opioid receptor antagonist, only rekindled hyperalgesia in the first 3 weeks of BMSC treatment. Focal downregulation of brainstem mu opioid receptors by RNA interference (RNAi) reversed the effect of BMSCs, when RNAi was introduced at 5- but not 1-week after BMSC transplantation. Thus, BMSCs produced long-term relief of pain and this effect involved activation of peripheral and central opioid receptors in distinct time domains. The findings prompt studies to elucidate the cellular mechanisms of the BMSC-induced pain relieving effect and translate these observations into clinical settings. STEM CELLS 2011;29:1294–1303