title: Platelet-derived growth factor receptor-β antagonism restores morphine analgesic potency against neuropathic pain.
abstract: 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
  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.
authors.affiliation: Department of Anesthesiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Donica
authors.affiliation: Department of Anesthesiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Shanping
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, The University of Texas - MD Anderson Cancer Center, Houston, Texas, United States of America; Department of Biochemistry and Molecular Biology, Genes and Development Graduate Program, The University of Texas - MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Howard B
authors.initials: HB
authors.lastname: Gutstein
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004347:Drug Interactions; D000068877:Imatinib Mesylate; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D009020:Morphine; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta