Feeling hot, feeling cold: TRP channels—a great story unfolds

Abstract

This editorial is about the roles that TRP channels play in heat and cold sensation and body temperature regulation. These roles may be exploited for therapeutic purposes (indeed, drugs targeting TRPV1, TRPA1 and TRPM8 channels are currently undergoing clinical trials for indications that range from pain through chronic cough and overactive bladder to cancer) or, conversely, may limit drug development (for example, several TRPV1 antagonists were withdrawn from clinical trials due to the hyperthermic reaction that they caused). In the future, modulation of thermosensitive TRP channels may ultimately find application in the treatment not only of pain, but also itch, stroke, asthma, and metabolic disorders. Of the multitude of targets involved in temperature sensation and body temperature regulation, why TRP channels? And why now?

Assessment of the TRPM8 inhibitor AMTB in breast cancer cells and its identification as an inhibitor of voltage gated sodium channels

“…TRPM8 is a member of the TRP ion channel family and is expressed in primary sensory neurons where it plays an important role in cold sensation (11). The properties of TRPM8 in specific neuronal sensory pathways have seen its identification as a target for a diverse range of conditions including pain, migraine and cough (12)(13)(14). However, despite the importance of TRPM8 as a sensor in neurons, it was actually first identified through a study assessing the overexpression of proteins in the prostate, which also demonstrated elevated levels in cancers of the prostate, lung, colon and breast (15).…”

NEO6860, modality-selective TRPV1 antagonist: a randomized, controlled, proof-of-concept trial in patients with osteoarthritis knee pain

“…Importantly, and despite the high exposure, none of the historical TRPV1 AEs (hyperthermia 9,16,33 and impaired noxious heat sensation 11,20,21 ) were observed in the NEO6860 group. It should be noted that with non–modality-selective TRPV1 antagonists, these 2 AEs were dose-dependent and reported in most (and sometimes in all) subjects at high exposure levels so that lack of such observations with NEO6860 is likely not attributable to the limited sample size of our studies (phase I and phase II).…”

A Capsaicin-Based Phytogenic Solution Improves Performance and Thermal Tolerance of Heat-Stressed Growing Pigs

“…The transient receptor potential type V member 1 (TRPV1) is the most abundant heat-activated non-selective cation channel in sensory neurons [ 48 ]. Importantly, capsaicin is considered to be the prototypical TRPV1 agonist and has pronounced effects on thermoregulation [ 49 , 50 ]. The activation of TRPV1 following capsaicin ingestion has been previously shown to lower body temperature and induce hypothermia [ 17 ].…”