Fig. 3

Effects of selective tropomyosin-receptor-kinase A (TrkA) inhibitor AR786 on carrageenan-induced joint inflammation. Rat knees were injected with either 2 % carrageenan (triangles and diamonds) or saline (circles) on day 0 (dotted line). Twice-daily oral doses of 30 mg/kg AR786 (diamonds) or 5 % Gelucire vehicle (triangles) control were given 1 h prior to and 8 h after the carrageenan injection and then twice daily (each pair of doses separated by 6 h) through day 4. Joint swelling (a) in carrageenan-injected knees was partially but significantly reduced following treatment with AR786 (diamonds) when compared to the vehicle-treated carrageenan-injected animals (triangles) (increased AUC over saline-injected, non-inflamed control knees 9.3 (95 % CI 8.4 to 10.1) mm/day versus 15.0 (95 % CI 13.4 to 16.6) mm/day, p < 0.001). Four days after carrageenan injection, macrophage infiltration (b) and synovial lining layer thickness/cellularity (c) were partially reduced, although synovial angiogenesis (endothelial cell (EC) proliferation index) (d) was not significantly affected in rats that were treated with AR786 compared with vehicle-treated, carrageenan-injected controls. **p < 0.01, ***p < 0.001 versus vehicle-treated carrageenan-injected animals; ⁺⁺ p < 0.01, ⁺⁺⁺ p < 0.001 versus saline-injected (non-synovitic) controls. Horizontal bars (c) represent median values