Platelet-Derived Growth Factor Receptor-β Antagonism Restores Morphine Analgesic Potency against Neuropathic Pain

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.