Figure 4.

Pazopanib, not vandetanib, suppressed the number of peripheral nerve fibers sprouting in the synovium-the role of VEGFR1 in sensory nerve distribution in synovium. Immunofluorescence (IF) assays were performed in histological sections of cartilage and synovial tissues in mice at 12 weeks post-partial medial meniscectomy (PMM). IA administration of drugs (Paz, Van) or vehicle (Veh, 5% DMSO in PBS) commenced at week 1 (Gp1, inflammatory pain stage), week 4 (Gp2, early OA stage) or week 8 (Gp3, advanced OA stage) after PMM twice per week for 12 weeks; and the effect of the drugs or vehicle on the expression of VEGFA (green), NGF (green) and PGP9.5 (green) in cartilage and/or synovium was examined by IF microscopy (A). Quantitative analysis showed that VEGFA, NGF and PGP9.5 expressions were significantly increased after PMM (n=3) (B-M). Statistical analysis was conducted using one-way ANOVA followed by the Tukey-Kramer test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 are for comparisons between groups with or without drug treatments in mice with PMM. 4′,6-diamidino-2-phenylindole (DAPI) stains nuclei blue. Scale bars: 100 μm. FI, fluorescence intensity; a.u., arbitrary unit.