TY - JOUR
T1 - Platelet-derived growth factor receptor-β antagonism restores morphine analgesic potency against neuropathic pain
AU - Donica, Courtney L.
AU - Cui, Yan
AU - Shi, Shanping
AU - Gutstein, Howard B.
PY - 2014/5/12
Y1 - 2014/5/12
N2 - 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-b 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.
AB - 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-b 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.
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U2 - 10.1371/journal.pone.0097105
DO - 10.1371/journal.pone.0097105
M3 - Article
C2 - 24820332
AN - SCOPUS:84901273551
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 5
M1 - e97105
ER -