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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Benzamides
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Chronic Pain / drug therapy*
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Dose-Response Relationship, Drug
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Drug Combinations
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Drug Tolerance / genetics*
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Fentanyl / pharmacology
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Glioma / drug therapy
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Imatinib Mesylate
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Morphine / administration & dosage*
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Morphine / adverse effects
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Morphine / therapeutic use
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Phosphorylation
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Piperazines / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Pyrimidines / pharmacology
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Rats
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Receptor, Platelet-Derived Growth Factor beta / genetics
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Receptor, Platelet-Derived Growth Factor beta / metabolism*
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / metabolism*
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Transcriptional Activation / drug effects*
Substances
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Benzamides
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Drug Combinations
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Receptors, Opioid, mu
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Morphine
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Imatinib Mesylate
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Receptor, Platelet-Derived Growth Factor beta
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Fentanyl