Osteoarthritis is the most common joint disease in the United States. It is a degenerative joint disease predominantly in the hands, hips, and knees, leading to a decrease in joint mobility. TRPV1 has 6 transmembrane domains, and a calcium-permeable pore is formed between the 5 th and 6 th domains . TRPV1 agonists bind to 2 residues located between the second loop and the S3 domain (Tyr 511 and Ser 512) and a residue beneath the 5 th domain (Tyr 550), creating the pore and allowing calcium cations to flow in .