Transient receptor potential cation channel subfamily V member 1 (TRPV1) and Transient receptor potential cation channel subfamily A member 1 (TRPA1) (TRPV1/TRPA1)

The TRPV1 and TRPA1 channels are non-selective cation channels belonging to the Transient Receptor Potential (TRP) superfamily, primarily expressed in nociceptive sensory neurons [1.4.1]. TRPV1, known as the capsaicin receptor, is activated by noxious heat (>43°C), low pH, and vanilloids, while TRPA1, the wasabi receptor, responds to noxious cold (<17°C) and various electrophilic irritants [1.3.1, 1.4.5]. These channels are frequently co-expressed and functionally interlinked, playing a critical role in the integration of painful stimuli and the mediation of neurogenic inflammation through the release of neuropeptides like CGRP and substance P [1.4.1, 1.4.4]. In disease states, they contribute to chronic pain, respiratory conditions like asthma and cough, and inflammatory skin disorders [1.2.1, 1.4.3]. Therapeutic strategies involve the development of dual antagonists to provide enhanced analgesic and anti-inflammatory effects compared to single-target agents [1.1.1, 1.2.2]. However, clinical development has faced significant challenges, such as TRPV1-mediated hyperthermia and the risk of impaired thermal sensation, which can lead to scalding injuries [1.1.1, 1.3.1].

Other names

Capsaicin receptorVanilloid receptor 1VR1Wasabi receptorAnkyrin-like protein with transmembrane domainsANKTM1OTRPC1

Antagonism of the ion channels to inhibit cation influx and subsequent neuronal depolarization, or desensitization through prolonged agonism [1.1.1, 1.4.3].