title: Blockade of PDGFR-β activation eliminates morphine analgesic tolerance.
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.
authors.affiliation: Department of Anesthesiology, The University of Texas-MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Katherine
authors.initials: K
authors.lastname: Barker
authors.forename: Shanping
authors.initials: S
authors.lastname: Shi
authors.forename: Miguel
authors.initials: M
authors.lastname: Diaz
authors.forename: Bing
authors.initials: B
authors.lastname: Mo
authors.forename: Howard B
authors.initials: HB
authors.lastname: Gutstein
mesh_terms: D000818:Animals; D001549:Benzamides; D059350:Chronic Pain / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004361:Drug Tolerance / Q000235:genetics*; D005283:Fentanyl / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy; D000068877:Imatinib Mesylate; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D001549:Benzamides; D004338:Drug Combinations; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D017450:Receptors, Opioid, mu; D009020:Morphine; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta; D005283:Fentanyl