Thermoreceptors

Thermosensation

Thermoreception is the sensation of temperature alterations. It serves as one of the most fundamental sensory functions across all species and is critical for survival. Environmental temperatures are detected as changes in skin temperature. A key process in thermoreception is the conversion of thermal energy into electrical signals, a process mediated by thermoreceptors sensitive to specific temperature ranges. It is often hard to distinguish thermoreception from other senses such as nociception; temperature sensation is carried along the same pathway as pain sensation..

Thermosensation is carried in the dorsal root ganglia (DRGs) and the trigeminal ganglia, housing the cell bodies of sensory neurons. The signal is then transmitted to the central targets of thermosensitive neurons lying in the dorsal horn of the spinal cord and the trigeminal nerve nuclei, where temperature information is processed. There, functionally distinct interneurons respond to specific sensory stimuli:

• "Cool" neurons respond to innocuous cool temperatures;
• "HPC" neurons respond to noxious heat, pinch and cold;
• "NS" (nociceptive specific) neurons respond to noxious heat and pinch;
• Rare "warm" neurons only respond to innocuous warm temperatures

In the dorsal horn, the sensory neurons synapse with second-order neurons, which then cross to the opposite side (decussate) and ascend tothe thalamus via the spinothalamic tract. In the thalamus (third-order neurons), the signal is further processed and relayed to the somatosensory cortex to be interpreted, integrated with other sensory data, and initiate appropriate responses such as moving away from a heat source.

Thermosensation begins with specific receptor intramembranous proteins located within free nerve endings in the skin. Thermoreceptors function with thermosensitive ion channels. When exposed to a certain temperature (e.g. placing your hand under the hot water in the shower), the cell membrane of the thermoreceptors changes its electrical state (voltage). The amount of change depends on the strength of the stimulus (how hot the water is). This is called a graded potential. The voltage change required to generate a signal is called the threshold, and the resulting electrical signal is known as an action potential. Local tissue temperature changes lead to opening of the channels, allowing ions to pass through. The area on the skin where a single receptor is sensitive to either hot or cold is called the receptive field of the thermoreceptor and it is approximately a few millimeters in size. Thermoreceptors are tonic receptors, meaning that they respond to a temperature stimulus for as long as it is present.

Thermoreceptors can detect both innocuous and noxious (thermal nociceptors) ranges. The temperature-detecting channels that belong to the TRP (transient receptor potential) superfamily are also known as ThermoTRP ion channels. These channels are classified into subfamilies, including:

• canonical (TRPC)
• melastatin (TRPM)
• ankyrin (TRPA)
• vanilloid (TRPV)

Some of these channels are activated by heat (TRPM2/3/4/5, TRPV1-4), while others by cold (TRPA1, TRPC5, TRPM8). Thermal TRP channels are polymodal receptors, i.e. activated in response to more than one type of stimuli such as temperature, voltage, pH, lipids, and agonists. They can also adjust their temperature threshold for evolutionary thermal adaptation, playing a crucial role in the environmental adaptation of species.

Noxious heat sensation

The transition from innocuous warmth to noxious heat is perceived at around 43°C . The ion channel operating as a receptor for noxious heat is TRPV1. The threshold of this channel is 42°C; higher temperature triggers an inward current in the TRPV1-expressing neurons. Additional noxious heat sensors include the TRPV2 (52°C threshold) and TRPM3 (40°C threshold) ion channels. Noxious heat also activates nociceptors.

Warm sensation

Warm receptors in the skin, responsible for detecting physiological temperature ranges are TRPV3, TRPV4 and TRPM2 ion channels. These channels are activated by temperatures over 27°C and under 42°C and are highly expressed in skin epidermal keratinocytes.

Cold sensation

The TRPM8 ion channel mediates the cold-induced current. TRPM8 can be activated by a broad range of cold temperatures, from innocuous (<26°C) to noxious cold ( <16°C), as well as by cooling compounds such as menthol. Noxious cold also activates nociceptors.

Chemical activation

Thermoreceptors can also be activated by chemical compounds that mimic temperature changes. For example, menthol (found in mint) activates cold-sensitive channels such as TRPM8, and capsaicin (found in chili peppers) can activate heat-sensitive channels like TRPV1. Extracellular protons can activate several ion channels, including TRPV1. In the absence of chemical agonists, these ion channels can be activated by their respective threshold temperatures.