Background/Purpose: In the gout, monosodium urate (MSU) crystals deposit intra-articularly and cause painful arthritis. In the present study we tested the hypothesis that Transient Receptor Potential Ankyrin 1 (TRPA1), an ion channel mediating nociceptive signals and neurogenic inflammation, is involved in MSU crystal-induced responses in gout by utilizing three experimental murine models.

Methods: The effects of pharmacological selective inhibition (HC-030031) and genetic depletion of TRPA1 were studied in MSU crystal-induced inflammation and pain by using 1) spontaneous weight-bearing test to assess MSU crystal-induced joint pain, 2) subcutaneous air-pouch model resembling joint inflammation to measure MSU crystal-induced cytokine production and inflammatory cell accumulation, and 3) MSU crystal -induced paw edema to assess acute vascular inflammatory responses and swelling.

Results: Intra-articularly injected MSU crystals provoked spontaneous weight shift off the affected limb in wild type but not in TRPA1 knock-out mice referring to alleviated joint pain in TRPA1 deficient animals. MSU crystal-induced cell infiltration and accumulation of cytokines MCP-1, IL-6, IL-1beta, MPO, MIP-1alpha and MIP-2 in subcutaneous air-pouch was attenuated in TRPA1 deficient mice and in mice treated with the TRPA1 inhibitor HC-030031 as compared to control animals. Further, HC-030031 treated and TRPA1 deficient mice developed tempered inflammatory edema when MSU crystals were injected into the paw.

Conclusion: TRPA1 mediates MSU crystal-induced inflammation and pain in experimental models introducing TRPA1 as a potential mediator and a drug target in gout flare.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urate-crystal-induced-inflammation-and-joint-pain-are-reduced-in-transient-receptor-potential-ankyrin-1-trpa1-deficient-mice-a-new-potential-role-for-trpa1-in-gout/