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TRPV1-Targeted Drugs in Development for Human Pain Conditions


The transient receptor potential vanilloid-1 (TRPV1) is a non-specific cation channel known for its sensitivity to pungent vanilloid compound (i.e. capsaicin) and noxious stimuli, including heat, low pH or inflammatory mediators. TRPV1 is found in the somatosensory system, particularly primary afferent neurons that respond to damaging or potentially damaging stimuli (nociceptors). Stimulation of TRPV1 evokes a burning sensation, reflecting a central role of the channel in pain. Pharmacological and genetic studies have validated TRPV1 as a therapeutic target in several preclinical models of chronic pain, including cancer, neuropathic, postoperative and musculoskeletal pain. While antagonists of TRPV1 were found to be a valuable addition to the pain therapeutic toolbox, their clinical use has been limited by detrimental side effects, such as hyperthermia. In contrast, capsaicin induces a prolonged defunctionalisation of nociceptors and thus opened the door to the development of a new class of therapeutics with long-lasting pain-relieving effects. Here we review the list of TRPV1 agonists undergoing clinical trials for chronic pain management, and discuss new indications, formulations or combination therapies being explored for capsaicin. While the analgesic pharmacopeia for chronic pain patients is ancient and poorly effective, modern TRPV1-targeted drugs could rapidly become available as the next generation of analgesics for a broad spectrum of pain conditions.

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Correspondence to Christophe Altier.

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This work was supported by operating grants from the Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (NSERC) [CA]. CA holds a Canada Research Chair in Inflammatory Pain. MD has an ACHRI (Alberta Children's Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship. No sponsor funding was received for the open access fee.

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MI and CA wrote the paper. MD designed the figure.

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Iftinca, M., Defaye, M. & Altier, C. TRPV1-Targeted Drugs in Development for Human Pain Conditions. Drugs 81, 7–27 (2021).

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