Transient receptor potential V1 (TRPV1) is specifically expressed in the nociceptive receptors and can detect a variety of noxious stimuli, thus potentiating pain sensitization. While peripheral delivery of capsaicin causes the desensitization of sensory neurons, thus alleviating pain. Therefore capsaicin is used in the clinical treatment of various types of pain; however, these treatments will bring many side effects, such as a strong burning pain in the early stages of treatment which hampers the further use of capsaicin. Thus, the studies of the functional regulation of TRPV1 are mainly focused on two aspects: to develop more potent analogues of capsaicin with less side effects; or to elucidate the mechanisms of TRPV1 in pain sensitivity, especially of that TRPV1 as a target of various protein kinases such as PKD1 and Cdk5 is involved pain hypersensitivity. Thus we would summarize the progress of these two aspects in this mini review.