Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal-related arthropathies

The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo. Delivery of air between the subcutaneous and dermal layer of the intra-scapular zone of the rodent generates an environment analogous to the synovial joint space. Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout, respectively. The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration, inflammatory cytokine production, eicosanoid release, complement activation and reactive oxygen species generation. Despite the utility of this model, great variation exists within the literature regarding the design, sampling time points, and endpoints measured. This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model. Standardizing the experimental approach would improve inter-study comparability, increase the internal validity of studies and reproducibility of results, and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.