The transient receptor potential vanilloid subfamily member 1 （TRPV 1） is a protein mainly expressed in sensory neurons and fibers, such as in trigeminal ganglion and dorsal root ganglion, and has been indicated to be involved in several physiological and pathological processes. Studies on thermal activation have revealed that phosphorylation is involved in TRPV1 activation and 2 putative phosphorylation sites, Ser residues 502 （Ser-502） and Set residues 800 （Ser-800）, have been recently confirmed to possess the capability of resensitizing TRPV 1. In addition to acidification, alkalization has also been proved to be a highly effective stimulator for TRPVI. TRPV1 could be regulated by various physical and chemical modulators, as well as the chronic pain. TRPV 1 plays a crucial role in the transmission of pain signals, especially under inflammation and the neoplasm conditions, and it can also modulate nociceptive afferents by reinforcing morphine tolerance. The present review mainly focused on the structural and functional complexities of TRPV1, together with its activation and modulation by a wide variety of physical and chemical stimuli. Its pharmacological manipulation （sensitization/desensitization） and therapeutical targets were also discussed.
