Abstract: Transient receptor potential vanilloid 1(TRPV1)is a nonselective cationic channel，and can be activted by capsaicin，protons and heat. TRPV1 plays a critical role in the initiation of neural inflammatory response and the pathway of pain signal transduction. As a new analgesics，TRPV1 antagonists block pain behaviors in models of inflammatory，neuropathic，and cancer pain. A number of pharmaceutical companies developed a range of TRPV1 antagonists with various structures. It was found that various chemotypes of TRPV1 antagonists would cause an increase in body temperature(hyperthermia)，which may become concerns for their development. This article summarizes the recent progress in TRPV1 antagonists development and the relevant hyperthermia.