Figure 1

Establishment of the SCW mono - arthritic multi - flare model. (A) Inflammation of the ankle joint followed over a 29 day period after administration of increasing doses (2.5 μg, 5 μg, or 10 μg) of SCW sensitization via i.a. delivery of antigen (day 1), followed by a systemic challenge (fixed dose 100 μg) on day 21. Values are mean ± SEM of 8-11 rats per group. (B) Bioluminescence imaging comparing non-arthritic and SCW rat ankle joint 6 hours following sensitization with 5 μg SCW. (C) Representative histomorphological sections of rat ankle joints collected on day 29 following SCW sensitization comparing Non-Arthritic and SCW rat paw. Points of interest are Tarsus (Ta), Tibia (Ti), slight inflammation (a), slight pannus (b), slight periosteal ossification (c), Synovium (S) and Articular cartilage (Ac). (D) Kinetics of cytokine expression in local injected ankle joint. Protein exudates were extracted from non-arthritic and arthritic ankle joints at various time points following i.a. sensitization of 5 μg of PGPS (Flare 1), and following systemic challenge of 100 μg PGPS (Flare 2). Levels of Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), Monocyte Chemotactic Protein-1 (MCP-1) and Cytokine-Induced Neutrophil Chemoattractant (CINC) were evaluated (shown from top left to lower right respectively). Values are mean ± SEM of 7-16 rats per group. δ Day 1 time point was at 6 hours post i.a. sensitization; α Day 21 time point was at 6 hours post i.v. challenge (E) Simultaneous evaluation of pain and inflammation. A composite of 4 independent studies showing inflammation (ankle diameter; Y axis) and pain (withdrawal threshold; Z axis) over time (days; X axis) following systemic i.v. challenge in Flare 2. Values are mean ± SEM of 6-8 rats per group. ** = P < 0.01 versus Non-Arthritic; *** = P < 0.001 versus Non-Arthritic.