TRPV1 Receptor Modulators: Emerging Therapies for Neuropathic, Osteoarthritic, and Perioperative Pain.

Capsaicin has proven itself to be a valuable addition to the pain therapeutic toolbox, but the development of other transient receptor potential vanilloid 1 (TRPV1)-targeted agents has been slow. As a multi-functional channel involved with various signaling pathways, TRPV1 has been challenging to target therapeutically while minimizing side effects. In addition to nociception, TRPV1 responds to temperature to aid thermoregulation and signals chemical responses to noxious environmental stimuli. There is still continued research and evolving structural understanding of the receptor given its complexity and integral function within the body's overall self-regulation. Both agonist and antagonist approaches are being actively explored to help treat patients with neuropathic and musculoskeletal pain. Promising pharmaceutical agonists for pain include low- and high-dose capsaicin formulations, resiniferatoxin, CNTX-4975, and vocacapsaicin. Potentially applicable antagonist drugs include NEO6860, Mavatrep, ACD-440, AJH-2947, DWP05195, and XEN-DO501. As our understanding of TRPV1 channels has continued to increase since the initial discovery, we are at last beginning to see some positive clinical developments for TRPV1 drugs in the realm of neuropathic, post-operative, musculoskeletal, and cancer pain.