PDGFR inhibition restores morphine efficacy against neuropathic pain.

<p>Animals underwent left L5 SNL as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097105#pone.0097105-Chung1" target="_blank">[11]</a>. Mechanical sensitivity was tested using von Frey filaments and 50% median response threshold determined <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097105#pone.0097105-Dixon1" target="_blank">[13]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097105#pone.0097105-Chaplan1" target="_blank">[14]</a>. Sham operated animals underwent the same surgical procedure except a suture was not tied around the L5 nerve root. (<b>A</b>) Baseline mechanical sensitivity was determined before surgery (BL). Animals then underwent SNL and were allowed to recover for two weeks. Mechanical sensitivity was tested to confirm that SNL induced mechanical allodynia (day 0). SNL animals received daily intrathecal (i.t.) injections of morphine (2 nmol), imatinib (10 µg), or the combination and mechanical sensitivity was determined. Sham operated animals received injections of vehicle alone. Neither morphine nor imatinib alone were analgesic. Co-administration of morphine and imatinib completely reversed SNL-induced mechanical allodynia. n = 8–9 per group. (<b>B</b>) Beginning the day after SNL, animals received daily subcutaneous (s.c.) injections of morphine (2.5 mg/kg), imatinib (5 mg/kg), morphine + imatinib or vehicle and mechanical sensitivity determined. Systemic co-administration of morphine and imatinib completely eliminated allodynia after nerve injury. n = 5–9 per group. (<b>C</b>) Following a two week recovery after SNL, animals received daily i.t. injections of morphine (2 nmol), PDGFR-β-Fc scavenger (500 ng), the combination or vehicle. While PDGFR-β-Fc had no effect on mechanical allodynia, co-administration of morphine and PDGFR-β-Fc completely restored the effectiveness of morphine. n = 7–10 per group. All data presented as grams +/− s.e.m; all p<0.0001 (2-way ANOVA).</p