Fig. 4.

Effect of repeated administration of CR6086, rofecoxib and tofacitinib in arthritic rats (collagen-induced arthritis [CIA] model). Arthritis was induced by intradermal injection of type II collagen as described in the Methods section of the main text. Three weeks later, animals were boosted. Oral treatments were administered daily (CR6086 and rofecoxib) or twice daily (tofacitinib), starting 3 days after boosting, and lasted 14 days. Paw volume (a and b) was measured 1 h after drug administration. Data represent the mean ± SEM of 12 rats/group. *P < 0.05 vs CIA rats treated with vehicle by two-way repeated-measures analysis of variance with Tukey’s multiple comparisons test. ^###P < 0.001 CIA vs sham animals at onset (day 0). c and d Box–and-whisker plots with the median histological scores assigned to the hind paws of each rat. ^aP < 0.0001, ^bP < 0.001, ^cP < 0.01, ^dP < 0.05 vs CIA rats treated with vehicle by Kruskal-Wallis test with Dunn’s multiple comparisons test