Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively non-selective cation permeability.
There are at least three types of receptors that are activated by cold, of which TRPM8 and TRPA1 are particularly sensitive. TRPM8 has a temperature sensitive range of about 10-26 oC (50-79 oF), and is largely associated with the perception of non-painful, or innocuous, cold. Menthol, a compound found in mint leaves, can also activate this receptor, which helps explain why this flavor is often perceived as cool. When temperatures are low enough to feel painful (i.e., noxious cold), TRPA1 receptors are activated. TRPA1 receptors respond to any temperature lower than 17 oC (~63 oF).
There are at least seven receptors that respond to heat. Of these, five respond to temperatures in the innocuous warmth range: TRPM2 (23-38 oC, or ~73-100oF), TRPC5 (26-38 oC, or ~79-100oF, TRPV4 (27-34 oC, or ~81-93 oF), TRPV3 (33-40 oC, or ~91-104 oF), and TRPM3 (> 40 oC, or 104 oF). Painful (i.e., noxious) heat is detected by TRPV1 receptors, which respond to temperatures greater than 42 oC (~108 oF). The TRPV1 receptor was first discovered because it responds well to capsaicin, a compound found in chili peppers. Like menthol and cold, capsaicin provides the perception of heat without changing the temperature. TRPV2 receptors respond to very hot and painful temperatures (i.e., extreme noxious heat), those greater than 52 oC (~126 oF).
Temperature information is transduced into electrical signals in the nerve endings. When nerves carry temperature information, the innocuous warm and cold information is kept separate until it reaches the brain. Cold signals are carried by dedicated myelinated Aδ fibers that perpetuate signals quickly, as well as slower, unmyelinated C-fibers. Warmth signals are carried by their own unmyelinated C-fibers. Like touch information, temperature information from the left side of the body is processed in the right brain hemisphere. The signal decussates in the spinal cord before being relayed to the hypothalamus. There, the information is used to regulate or adjust bodily functions, like shivering or sweating. Innocuous warm and cold signals are finally relayed to several cortical areas—notably the orbitofrontal cortex.
Painful temperature information takes a separate path, using C and Aδ fibers that are not temperature specific and can carry both hot and cold signals. Like innocuous temperature signals, they decussate in the spinal cord and are sent to the hypothalamus. From the hypothalamus, the information is sent to the anterior cingulate cortex, which generates the perception of painful cold or hot.
Studies suggest that individuals first consciously detect a feeling of coldness and warmness at about 31 oC and 34 oC, respectively. The range between 31o and 34o is similar to the surface temperature of the skin and may not be noticeable. Pain from coldness and heat is perceived at temperatures of about <12 oC and >45 oC, respectively.
