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Blockade of PDGFR-β activation eliminates morphine analgesic tolerance

Nature Medicine volume 18, pages 385–387 (2012)Cite this article

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Abstract

For centuries, opioid drugs have been the mainstay of chronic pain treatment. However, over time analgesic tolerance develops, leaving few treatment options. Here we show that platelet-derived growth factor receptor-β (PDGFR-β)-mediated signaling plays a key role in morphine tolerance. PDGFR-β inhibition selectively eliminates morphine tolerance in rats. PDGFR-β inhibitors are widely used and well tolerated, suggesting that clinical translation of our findings could reduce the suffering endured by individuals with intractable pain.

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Figure 1: Morphine activates the PDGFR-β, and PDGFR-β inhibition blocks tolerance.
Figure 2: Imatinib reverses morphine tolerance, and its effects are mediated by PDGFR-β.

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Acknowledgements

We thank J. Dulin, T. Sylvester and C. Schultz for technical support. This work was funded by grants from the US National Institute on Drug Abuse R01DA15146 and the US National Institute on Alcohol Abuse and Alcoholism R01AA16157 to H.B.G. We dedicate this work to the memory of our colleague and dear friend Bing Mo, who tragically passed away before these studies were completed.

Author information

Author notes

  1. Bing Mo: Deceased.

  2. Yan Wang and Katherine Barker: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, The University of Texas–MD Anderson Cancer Center, Houston, Texas, USA

    Yan Wang, Katherine Barker, Shanping Shi, Miguel Diaz, Bing Mo & Howard B Gutstein

  2. Department of Biochemistry and Molecular Biology, The University of Texas–MD Anderson Cancer Center, Houston, Texas, USA

    Yan Wang, Katherine Barker, Shanping Shi, Miguel Diaz, Bing Mo & Howard B Gutstein

  3. Genes and Development Graduate Program, The University of Texas–MD Anderson Cancer Center, Houston, Texas, USA

    Howard B Gutstein

Authors
  1. Yan Wang
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  2. Katherine Barker
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  3. Shanping Shi
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  4. Miguel Diaz
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  5. Bing Mo
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  6. Howard B Gutstein
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Contributions

Y.W., K.B., S.S., M.D. and B.M. performed experiments and analyzed data. H.B.G. conceived and designed all experiments, interpreted results and wrote the manuscript.

Corresponding author

Correspondence to Howard B Gutstein.

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The authors declare no competing financial interests.

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Supplementary Figures 1–11 and Supplementary Methods (PDF 1478 kb)

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Wang, Y., Barker, K., Shi, S. et al. Blockade of PDGFR-β activation eliminates morphine analgesic tolerance. Nat Med 18, 385–387 (2012). https://doi.org/10.1038/nm.2633

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