Trends in pharmacological sciences
-
Cloning of the transient receptor potential vanilloid type 1 (TRPV1), the heat-gated cation channel/capsaicin receptor expressed by sensory neurons, has opened the door for development of new types of analgesics that selectively act on nociceptors. Here we summarize mutagenetic evidence for selective loss of responsiveness to vanilloids, protons, and heat stimuli to provide clues for avoiding on-target side effects of hyperthermia and burn risk. ⋯ Several endogenous lipid ligands activate and inhibit TRPV1 and its gating initiates sensory transducer and mediator-releasing functions. Second generation TRPV1 antagonists that do not induce hyperthermia are under development, and a dermal capsaicin patch is already on the market for long-term treatment of neuropathic pain.