Blockade of PDGFR-β activation eliminates morphine analgesic tolerance

Nat Med. 2012 Feb 19;18(3):385-7. doi: 10.1038/nm.2633.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzamides
  • Chronic Pain / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Tolerance / genetics*
  • Fentanyl / pharmacology
  • Glioma / drug therapy
  • Imatinib Mesylate
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Morphine / therapeutic use
  • Phosphorylation
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / metabolism*
  • Transcriptional Activation / drug effects*

Substances

  • Benzamides
  • Drug Combinations
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptors, Opioid, mu
  • Morphine
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor beta
  • Fentanyl