Animals will be given intra-articular injections into one tibia-tarsal (ankle) joint with 10 µl (mice) or 30 µl (rats) of monosodium urate (MSU) crystals (25 mg/ml) or PBS.
Disease Parameters/Progression:
Significant swelling in the ankle is seen by 12 hour post injection and remains elevated out to 3 days post injection. An increase in foot sensitivity, as measured by von Frey filaments, occurs by 24 hours post injection and continues to day 3. Weight differences are also seen in the MSU injected paw versus PBS.
Dosing Paradigms:
Prophylactic (Developing) – Dose prior to MSU injection.
Established (Therapeutic) – Dose after MSU injection and continue for 3 days.
Route of administration: SC, PO, IP, IV
Clinical Assessment:
Animals are observed daily for significant clinical signs, moribundity and mortality. Body weights and caliper measurements will be taken. Von Frey assessment of pain can be performed.
Histopathological Assessment:
Histopathology may also be done.
Sample Data (Click on image to enlarge):
Mouse Clinical
Rat Clinical
Notes:
Current treatments of gout include nonsteroidal anti-inflammatory drugs (NSAIDSs), steroids, or colchicine. For some patients these treatments may not be effective in treating gout or have adverse side effects1,2. The MSU-induced inflammation model provides a good, simple screening tool to test compounds, and to further understand the complex interplay of inflammation and pain.
Optional Endpoint
PK/PD blood collections
Cytokine/chemokine analysis via Luminex(R)
Other sandwich ELISAs
CBC/clinical chemistry analysis
Soft tissue collection
Histopathologic analysis
Immunohistochemistry analysis
References
Sabina EP, Chandel S, and Rasool MK. Inhibition of monosodium rate crystal-induced inflammation by withaferin A. J Pharm Pharmaceut Sci. 2008; 11(4):46-55.
Getting SJ, et al. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis & Rheumatism. 2002; 46(10):2765-2775.
Torres R, et al. Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann. Rheum Dis. 2009; 68(10):1602-1608.
For more information about MSU-Induced Arthritis (Mice and Rats), contact us here.
