What are TRP channels?
TRP channels are a large family of transient receptor potential channels that allow ions to flow in response to a variety of stimuli, including temperature, many plant-derived compounds, and endogenous molecules. Different TRP channels cover the range of temperatures sensed by afferent fibers. For example, the threshold for TRPV1 is approximately 43 to 45 °C, which is close to the threshold for evoking heat pain. TRPV3 responds to warm temperatures. TRPM8 responds to cooling. TRPA1 responds to irritants.
Capsaicin is the exogenous stimulus that binds TRPV1. Camphor binds TRPV3; wasabi, mustard oil, garlic, and cinnamaldehyde bind TRPA1. We have little information about the endogenous chemical ligands that activate these channels. However, there is evidence that bradykinin, via an action at the B2 subtype of G protein–coupled receptor, regulates the properties of the TRPV1 and TRPA1 receptors.
Importantly, the properties of the channels are altered in the setting of injury. For example, TRPV1 not only responds to capsaicin and noxious heat but also is regulated by pH. In the setting of tissue injury, where pH is lowered, the threshold for opening the channel is reduced sufficiently so that normally innocuous temperatures can evoke action potentials in nociceptors that express TRPV1. Studies in animals indicate that the pain of bone metastasis is significantly attenuated in animals in which TRPV1 is deleted genetically.