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

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 neuropa...

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Bibliographic Details
Published in:PloS one 2014-05, Vol.9 (5), p.e97105
Main Authors: Donica, Courtney L, Cui, Yan, Shi, Shanping, Gutstein, Howard B
Format: Article
Language:English
Subjects:
Analgesics
Analgesics - pharmacology
Analgesics - therapeutic use
Anesthesiology
Animals
Benzamides - pharmacology
Biology and Life Sciences
Cancer therapies
Chronic pain
Drug dosages
Drug Interactions
Drug tolerance
Growth factors
Imatinib
Imatinib Mesylate
Inhibition
Injuries
Male
Medicine and Health Sciences
Morphine
Morphine - pharmacology
Morphine - therapeutic use
Narcotics
Nerves
Nervous system
Neuralgia
Neuralgia - drug therapy
Neuropathy
Opiates
Opioids
Pain
Pandemics
Piperazines - pharmacology
Platelet-derived growth factor
Pyrimidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors
Rodents
Signal transduction
Variance analysis
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Summary: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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0097105