Spinal blockade of vascular endothelial growth factor A (VEGF-A)/vascular endothelial growth factor receptor 2 (VEGFR2) suppresses tumor-induced NMDA receptor activation and proinflammatory cytokine production via protein kinase C (PKC) and Src family kinase (SFK), respectively. (A to D) Western blot analysis shows that VEGF-A neutralizing antibody, ZM 323881, or GF109203X significantly attenuated tumor-induced upregulation of phospho- (p-)NMDA receptor subunit 2B (NR2B) (A), p-extracellular signal-regulated kinase (ERK)1/2 (B), p-calcium/calmodulin-dependent protein kinase II (CaMKII) (C), and p-cyclic-AMP response element-binding protein (CREB) (D) protein expression in the spinal dorsal horn. (E to H) Real-time quantitative polymerase chain reaction analysis shows that VEGF-A neutralizing antibody, ZM 323881, or PP2 significantly attenuated tumor-induced upregulation of Tnf-α (E), Il-1β (F), Il-6 (G), and Il-18 (H) mRNA expression in the spinal dorsal horn. (A to H) VEGF-A neutralizing antibody (Ab; 2 μg, intrathecal), ZM 323881 (ZM, 100 nM, intrathecal), GF109203X (GFX, 0.2 μg, intrathecal), or PP2 (10 μg, intrathecal) was injected once daily on days 12, 13, and 14 post–tumor inoculation. Tissues were collected 4 h after the last injection on day 14. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01 versus sham group; ^#P < 0.05, ^##P < 0.01 versus tumor group, N = 4 (A-D) or 5 (E to H) for each group, one-way ANOVA with post hoc Dunnett test.