Involvement of TRPA1 in ET-1-induced pain-like behavior in mice.

Transient receptor potential ankyrin subfamily member 1 (TRPA1) is a nonselective cation channel known as a noxious cold-activated ion channel. Recent findings implicated its involvement in acute and chronic cold nociception processes. Here, we investigated whether TRPA1 is involved in endothelin-1 (ET-1)-induced spontaneous pain-like behavior in C57BL/6J mice. We found that TRPA1 antagonists, HC-030031 and AP18, significantly reduced the pain-like behavior caused by ET-1. AP18 also significantly reduced the pain caused by cinnamaldehyde, an agonist of TRPA-1. However, AP18 did not alleviate the pain caused by capsaicin. The pain-like behavior caused by ET-1 was inhibited by phospholipase C inhibitor, but not by protein kinase C inhibitor. Low dose of ET-1 could potentiate cinnamaldehyde-induced nociception. Our results suggested that TRPA1 is involved in ET-1-induced spontaneous pain-like behavior in mice.