Pyrazine-fused triterpenoids block TRPA1 ion channel in vitro and inhibit TRPA1-mediated inflammation in vivo

Background: TRPA1 is a cation channel expressed mostly in non-myelinated nerve endings. TRPA1 has a significant role in sensing chemical and mechanical pain and, according to the more recent findings, also in inflammation. We have recently shown that pharmacological blockade and genetic deletion of TRPA1 alleviates inflammation and pain in murine models of gout and (osteo)arthritis. Furthermore, we have discovered that TRPA1 is expressed in human articular chondrocytes and synovial cells in inflammatory conditions, and mediates inflammatory and catabolic responses in vitro.