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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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.
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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.
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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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DOI: https://doi.org/10.1038/nm.2633
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