The TRPV1 receptor is known to play a role in nociceptive transmission in multiple organ systems, usually in response to the pain of inflammation. TRPV1 antagonism has so far shown limited benefit in antinociception. Capsaicin, a TRPV1 agonist, has been shown to induce a refractory period in the nerve terminal expressing TRPV1 and even, in sufficient dosing, to create long-term nerve terminal defunctionalization. This has led to research into topical capsaicin as a treatment for multiple painful conditions. The majority of work has focused on musculoskeletal pain and neuropathic pain and has revealed that although low-dose topical capsaicin has limited effectiveness as an analgesic, high-dose capsaicin, when tolerated, has the potential for long-term analgesia in certain types of neuropathic pain.