Multimodal Interactions: Thermal-Chemical

Thermal Sensitivity

The ability to sense and respond to environmental temperatures is critical for human survival. As external temperatures increase or decrease, thermal changes are detected by receptors in the cell membranes of thermosensitive nerve cells. These cells are found throughout the body, including peripheral tissues like skin and muscle, as well as in the mucous membranes of the oral and nasal cavities. Detection of temperature changes by these receptors causes a rapid excitation of the nerve cell, and this signal is conveyed to the brain, where it is ultimately interpreted as heat or cold. However, as temperatures (measured here in Celsius, C) exceed a certain threshold and become too hot (∼41 °C) or too cold (∼4 °C), the stimulus is additionally perceived as painful. It is now known that thermal sensitivity is due to the existence of specific protein receptors that are tuned to respond to specific temperatures. To date, six receptor proteins that respond to thermal stimuli have been identified. Each of these proteins responds to a specific temperature range. For instance, the protein TRPM8 (transient receptor potential melastatin-type 8) has been shown to respond to cool temperatures between 8 to 28 °C, whereas a different protein, TRPV3 (transient receptor potential vanilloid-type 3), has been shown to respond to warm temperatures between 32 to 37 °C. Collectively, these proteins respond to temperatures that vary in range from 4 to 53 °C and form a sort of physiological thermometer. Table 1 lists all of the known protein receptors that respond to thermal stimuli and the temperature ranges that activate them.

The receptor proteins that respond to temperatures are found in two types of temperature-sensitive cells—those that respond to nonpainful temperatures and those that respond to painfully hot or cold temperatures. Cells that respond to painful stimuli are called nociceptors and express the receptor proteins that are activated by potentially harmful temperatures (TRPA1, TRPV1, TRPV2). Cells that respond to nonpainful thermal stimuli can be subdivided into cold-sensitive and warm-sensitive populations. Cold-sensitive cells exclusively express receptor proteins that are activated by cool temperatures (TRPM8), whereas warm-sensitive cells express proteins sensitive to warm, but not hot, temperatures (TRPV3, TRPV4). Although this organization provides the molecular and neural basis for temperature perception and discrimination, it fails to explain how chemicals can similarly evoke heat, cold, and pain sensations.

...