Platelet-derived growth factor receptor-β antagonism restores morphine analgesic potency against neuropathic pain

PLoS One. 2014 May 12;9(5):e97105. doi: 10.1371/journal.pone.0097105. eCollection 2014.


Background: Chronic, intractable pain is a problem of pandemic proportions. Pain caused by nerve injuries (neuropathic pain) is extremely difficult to treat. For centuries, opiates such as morphine have been the first-line treatment for severe chronic pain. However, opiates are often ineffective against neuropathic pain, leaving few options for suffering patients. We previously demonstrated that platelet-derived growth factor- β (PDGFR-β) inhibition completely eliminated morphine tolerance. In these studies, we determined whether PDGFR-β inhibition could improve the effectiveness of morphine for neuropathic pain treatment.

Results and findings: Spinal nerve ligation was performed in male Sprague-Dawley rats. The clinically used PDGFR antagonist imatinib did not relieve mechanical pain in a nerve injury model as determined by Von Frey assay. Surprisingly, combining imatinib with a previously ineffective dose of morphine led to complete pain relief. Scavenging released PDGF-B also markedly augmented the analgesic effect of morphine.

Conclusions: These findings suggest the novel hypothesis that PDGF-B released by injured nerves renders animals resistant to morphine, implying that PDGFR-β inhibition could potentially eliminate the tremendous suffering caused by neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Benzamides / pharmacology*
  • Drug Interactions
  • Imatinib Mesylate
  • Male
  • Morphine / pharmacology*
  • Morphine / therapeutic use
  • Neuralgia / drug therapy*
  • Piperazines / pharmacology*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors*


  • Analgesics
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Morphine
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor beta