This topic is a classic example of GENE-ENVIRONMENT INTERACTIONS. All animals, including humans, “know” when they’re too cold or when they get too hot; they sense these cues/signals from the environment. This includes even microbes that are mobile: they will “move toward” or “move away” from a heat signal. The genetic predisposition of the animal –– as far as how it handles these signals –– of course comes from the DNA (genes). In mammals, this ability is mediated by specialized heat-sensitive neurons of the somatosensory system that innervate the skin. These neurons are fine-tuned to detect the temperature at which pleasurable warmth turns into painful (noxious) heat, at which time the animal will initiate protective reflexes, triggering avoidance behaviors.
Transient receptor potential (TRP) channels are a group of ion-channel proteins located mostly on the plasma membrane of numerous mammalian cell-types. The human and mouse genomes contain about 28 TRP genes, encoding proteins that share some structural similarity to one other. These are grouped into two broad categories, which mediate a variety of sensations such as pain, noxious heat, warmth or coldness, pressure, and vision. Authors [see attached article] report, in mouse studies, that three TRP channels work together to detect noxious heat.
The first temperature-sensitive TRP channel (TRPV1) was discovered more than 20 years ago; TRPV1 exhibited a crucial role in the development of hypersensitivity to heat after injury or inflammation, but experiments with mice lacking the Trpv1 gene display only a partial defect in their ability to sense and respond to noxious heat. TRPM3 was then shown to be activated in response to painful temperatures; however, heat-evoked pain-avoidance behaviors are only partially attenuated in mice that lacked this channel gene. Authors show herein that acute noxious heat-sensing in mice depends on a trio of TRP in channels: TRPV1, TRPM3, and TRPA1.
Although some degree of somatosensory heat responsiveness at the cellular and behavioral levels is seen when only one of these three TRP channels is functional –– the combined elimination of all three channels [studying Trpv1/Trpm3/Trpa1(−/−) triple-knockout (TKO) mice] largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing specific forms of sensory nerve fibers that innervate the skin. However, the normal responses to cold or mechanical stimuli, as well as a preserved preference for moderate temperatures, remain intact. These data indicate that initiation of the acute heat-evoked pain response in sensory nerve endings relies on three functionally-redundant TRP channels –– representing a fault-tolerant mechanism to avoid burn injury.
Nature 29 Mar 2o18; 555: 662–666 & News-N-Views 591–592