Thermoreceptor

Last updated September 14, 2023

A thermoreceptor is a non-specialised sense receptor, or more accurately the receptive portion of a sensory neuron, that codes absolute and relative changes in temperature, primarily within the innocuous range. In the mammalian peripheral nervous system, warmth receptors are thought to be unmyelinated C-fibres (low conduction velocity), while those responding to cold have both C-fibers and thinly myelinated A delta fibers (faster conduction velocity).^[1]^[2] The adequate stimulus for a warm receptor is warming, which results in an increase in their action potential discharge rate. Cooling results in a decrease in warm receptor discharge rate. For cold receptors their firing rate increases during cooling and decreases during warming. Some cold receptors also respond with a brief action potential discharge to high temperatures, i.e. typically above 45 °C, and this is known as a paradoxical response to heat. The mechanism responsible for this behavior has not been determined.

Location

In humans, along the axons of Lissauer's tract temperature or pressure sensations enter the spinal cord. The Lissauer's tract will synapse on first-order neurons in grey matter of the dorsal horn, one or two vertebral levels up. The axons of these second-order neurons then decussate, joining the spinothalamic tract as they ascend to neurons in the ventral posterolateral nucleus of the thalamus.

In mammals, temperature receptors innervate various tissues including the skin (as cutaneous receptors), cornea and urinary bladder. Neurons from the pre-optic and hypothalamic regions of the brain that respond to small changes in temperature have also been described, providing information on core temperature. The hypothalamus is involved in thermoregulation, the thermoreceptors allowing feed-forward responses to a predicted change in core body temperature in response to changing environmental conditions.

Structure

Thermoreceptors have been classically described as having free –non-specialized– endings.^[3] The mechanism of activation in response to temperature changes is not completely understood.

Function

Cold-sensitive thermoreceptors give rise to the sensations of cooling, cold and freshness. In the cornea cold receptors are thought to respond with an increase in firing rate to cooling produced by evaporation of lacrimal fluid 'tears' and thereby to elicit a blink reflex. Other thermoreceptors will react to opposite triggers and give rise to heat and in some cases even burning sensations. This is often experienced when coming in contact with capsaicin, an active chemical commonly found in chili peppers. When coming in contact with your tongue (or any internal surface), the capsaicin de-polarizes the nerve fibers, allowing sodium and calcium into the fibers. In order for fibers to do so, they must have a specific thermoreceptor. The thermoreceptor reacting to capsaicin and other heat producing chemicals is known as TRPV1. In response to heat, the TRPV1 receptor opens up passages that allow ions to pass through, causing the sensation of heat or burning. TRPV1 also has a molecular cousin, TRPM8. Unlike TRPV1, TRPM8 produces cooling sensations as mentioned previously. Similar to TRPV1, TRPM8 responds to a certain chemical trigger by opening its ion pathways. In this case, the chemical trigger is often menthol or other cooling agents. Studies performed on mice determined that the presence of both these receptors allows for a gradient of temperature sensing. Mice lacking the TRPV1 receptor were still capable of determining areas significantly colder than on a heated platform. Mice lacking the TRPM8 receptor however, were not able to determine the difference between a warm platform and a cold platform, suggesting we rely on TRPM8 to determine cold feelings and sensations.^[4]

Distribution

Warm and cold receptors play a part in sensing innocuous environmental temperature. Temperatures likely to damage an organism are sensed by sub-categories of nociceptors that may respond to noxious cold, noxious heat or more than one noxious stimulus modality (i.e., they are polymodal). The nerve endings of sensory neurons that respond preferentially to cooling are found in moderate density in the skin but also occur in relatively high spatial density in the cornea, tongue, bladder, and facial skin. The speculation is that lingual cold receptors deliver information that modulates the sense of taste; i.e. some foods taste good when cold, while others do not.^[5]

Mechanism of transduction

This area of research has recently received considerable attention with the identification and cloning of the Transient Receptor Potential (TRP) family of proteins. The transduction of temperature in cold receptors is mediated in part by the TRPM8 channel. This channel passes a mixed inward cationic (predominantly carried by Na⁺ ions although the channel is also permeable to Ca²⁺) current of a magnitude that is inversely proportional to temperature. The channel is sensitive over a temperature range spanning about 10-35 °C. TRPM8 can also be activated by the binding of an extracellular ligand. Menthol can activate the TRPM8 channel in this way. Since the TRPM8 is expressed in neurons whose physiological role is to signal cooling, menthol applied to various bodily surfaces evokes a sensation of cooling. The feeling of freshness associated with the activation of cold receptors by menthol, particularly those in facial areas with axons in the trigeminal (V) nerve, accounts for its use in numerous toiletries including toothpaste, shaving lotions, facial creams and the like.

Another molecular component of cold transduction is the temperature dependence of so-called leak channels which pass an outward current carried by potassium ions. Some leak channels derive from the family of two-pore (2P) domain potassium channels. Amongst the various members of the 2P-domain channels, some close quite promptly at temperatures less than about 28 °C (e.g. KCNK4(TRAAK), TREK). Temperature also modulates the activity of the Na⁺/K⁺-ATPase. The Na⁺/K⁺-ATPase is a P-type pump that extrudes 3Na⁺ ions in exchange for 2K⁺ ions for each hydrolytic cleavage of ATP. This results in a net movement of positive charge out of the cell, i.e. a hyperpolarizing current. The magnitude of this current is proportional to the rate of pump activity.

It has been suggested that it is the constellation of various thermally sensitive proteins together in a neuron that gives rise to a cold receptor.^[6] This emergent property of the neuron is thought to comprise, the expression of the aforementioned proteins as well as various voltage-sensitive channels including the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel and the rapidly activating and inactivating transient potassium channel (IK_A).

Related Research Articles

Nociception is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal to trigger an appropriate defensive response.

Thermoception or thermoreception is the sensation and perception of temperature, or more accurately, temperature differences inferred from heat flux. It deals with a series of events and processes required for an organism to receive a temperature stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response.

<span class="mw-page-title-main">Sensory nervous system</span> Part of the nervous system responsible for processing sensory information

The sensory nervous system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory neurons, neural pathways, and parts of the brain involved in sensory perception and interoception. Commonly recognized sensory systems are those for vision, hearing, touch, taste, smell, balance and visceral sensation. Sense organs are transducers that convert data from the outer physical world to the realm of the mind where people interpret the information, creating their perception of the world around them.

In physiology, a stimulus is a detectable change in the physical or chemical structure of an organism's internal or external environment. The ability of an organism or organ to detect external stimuli, so that an appropriate reaction can be made, is called sensitivity (excitability). Sensory receptors can receive information from outside the body, as in touch receptors found in the skin or light receptors in the eye, as well as from inside the body, as in chemoreceptors and mechanoreceptors. When a stimulus is detected by a sensory receptor, it can elicit a reflex via stimulus transduction. An internal stimulus is often the first component of a homeostatic control system. External stimuli are capable of producing systemic responses throughout the body, as in the fight-or-flight response. In order for a stimulus to be detected with high probability, its level of strength must exceed the absolute threshold; if a signal does reach threshold, the information is transmitted to the central nervous system (CNS), where it is integrated and a decision on how to react is made. Although stimuli commonly cause the body to respond, it is the CNS that finally determines whether a signal causes a reaction or not.

A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception.

Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal ganglia of the spinal cord.

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

Chemesthesis is the chemical sensitivity of the skin and mucous membranes. Chemesthetic sensations arise when chemical compounds activate receptors associated with other senses that mediate pain, touch, and thermal perception. These chemical-induced reactions do not fit into the traditional sense categories of taste and smell.

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. And a receptor being clearly present in bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes, and fatty acid metabolites with affinity for this CB receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA).

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

<span class="mw-page-title-main">Capsazepine</span> Chemical compound

Capsazepine is a synthetic antagonist of capsaicin. It is used as a biochemical tool in the study of TRPV ion channels.

Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and B are myelinated. Group C fibers include postganglionic fibers in the autonomic nervous system (ANS), and nerve fibers at the dorsal roots. These fibers carry sensory information.

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

The axon reflex is the response stimulated by peripheral nerves of the body that travels away from the nerve cell body and branches to stimulate target organs. Reflexes are single reactions that respond to a stimulus making up the building blocks of the overall signaling in the body's nervous system. Neurons are the excitable cells that process and transmit these reflex signals through their axons, dendrites, and cell bodies. Axons directly facilitate intercellular communication projecting from the neuronal cell body to other neurons, local muscle tissue, glands and arterioles. In the axon reflex, signaling starts in the middle of the axon at the stimulation site and transmits signals directly to the effector organ skipping both an integration center and a chemical synapse present in the spinal cord reflex. The impulse is limited to a single bifurcated axon, or a neuron whose axon branches into two divisions and does not cause a general response to surrounding tissue.

David Jay Julius is an American physiologist and Nobel Prize laureate known for his work on molecular mechanisms of pain sensation and heat, including the characterization of the TRPV1 and TRPM8 receptors that detect capsaicin, menthol, and temperature. He is a professor at the University of California, San Francisco.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.

Vampire bats have developed a specialized system using infrared-sensitive receptors on their nose-leaf to prey on homeothermic (warm-blooded) vertebrates. Trigeminal nerve fibers that innervate these IR-sensitive receptors may be involved in detection of infrared thermal radiation emitted by their prey. This may aid bats in locating blood-rich areas on their prey. In addition, neuroanatomical and molecular research has suggested possible similarities of IR-sensing mechanisms between vampire bats and IR-sensitive snakes. Infrared sensing in vampire bats has not yet been hypothesized to be image forming, as it was for IR-sensitive snakes. While the literature on IR-sensing in vampire bats is thin, progress continues to be made in this field to identify how vampire bats can sense and use infrared thermal radiation.

RhTx is a small peptide toxin from Scolopendra subspinipes mutilans, also called the Chinese red-headed centipede. RhTx binds to the outer pore region of the temperature regulated TRPV1 ion channel, preferably in activated state, causing a downwards shift in the activation threshold temperature, which leads to the immediate onset of heat pain.

WS-12 is a chemical compound that acts as a potent and selective activator of the TRPM8 calcium channel, which is responsible for the sensation of coldness produced by menthol. It is slightly less potent as a TRPM8 activator compared to icilin, but is much more selective for TRPM8 over related calcium channels. It produces analgesic and antiinflammatory effects in animal models with similar efficacy to menthol and a reduced side effect profile.

References

↑ Darian-Smith I, Johnson KO, LaMotte C, Shigenaga Y, Kenins P, Champness P (1979). "Warm fibers innervating palmar and digital skin of the monkey: responses to thermal stimuli" . Journal of Neurophysiology (Article). 42 (5): 1297–1315. doi:10.1152/jn.1979.42.5.1297. PMID 114608.
↑ Torebjörk, ERIK; Schmelz, MARTIN (2005-01-01), Dyck, Peter J.; Thomas, P. K. (eds.), "Chapter 38 - Single-Unit Recordings of Afferent Human Peripheral Nerves by Microneurography", Peripheral Neuropathy (Fourth Edition), Philadelphia: W.B. Saunders, pp. 1003–1014, ISBN 978-0-7216-9491-7 , retrieved 2023-06-21
↑ Eliav, Eli; Gracely, Richard H (2008-01-01), Sharav, Yair; Benoliel, Rafael (eds.), "Chapter 3 - Measuring and assessing pain", Orofacial Pain and Headache, Edinburgh: Mosby, pp. 45–56, ISBN 978-0-7234-3412-2 , retrieved 2023-09-13
↑ Zhang, Xuming (2015). "Molecular sensors and modulators of thermoreception". Channels (Review). Taylor & Francis. 9 (2): 73–81. doi:10.1080/19336950.2015.1025186. eISSN 1933-6969. PMC 4594430 . PMID 25868381.
↑ "Why Does Food Taste Different When It's Cold Vs. When It's Hot?". Science ABC. 2017-04-22. Retrieved 2023-09-06.
↑ Viana F, de la Peña E, Belmonte C (2002). "Specificity of cold thermotransduction is determined by differential ionic channel expression" . Nature Neuroscience . 5 (3): 254–260. doi:10.1038/nn809. PMID 11836533. S2CID 21291629.

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[1] Darian-Smith I, Johnson KO, LaMotte C, Shigenaga Y, Kenins P, Champness P (1979). "Warm fibers innervating palmar and digital skin of the monkey: responses to thermal stimuli" . Journal of Neurophysiology (Article). 42 (5): 1297–1315. doi:10.1152/jn.1979.42.5.1297. PMID 114608.

[2] Torebjörk, ERIK; Schmelz, MARTIN (2005-01-01), Dyck, Peter J.; Thomas, P. K. (eds.), "Chapter 38 - Single-Unit Recordings of Afferent Human Peripheral Nerves by Microneurography", Peripheral Neuropathy (Fourth Edition), Philadelphia: W.B. Saunders, pp. 1003–1014, ISBN 978-0-7216-9491-7 , retrieved 2023-06-21

[3] Eliav, Eli; Gracely, Richard H (2008-01-01), Sharav, Yair; Benoliel, Rafael (eds.), "Chapter 3 - Measuring and assessing pain", Orofacial Pain and Headache, Edinburgh: Mosby, pp. 45–56, ISBN 978-0-7234-3412-2 , retrieved 2023-09-13

[4] Zhang, Xuming (2015). "Molecular sensors and modulators of thermoreception". Channels (Review). Taylor & Francis. 9 (2): 73–81. doi:10.1080/19336950.2015.1025186. eISSN 1933-6969. PMC 4594430 . PMID 25868381.

[5] "Why Does Food Taste Different When It's Cold Vs. When It's Hot?". Science ABC. 2017-04-22. Retrieved 2023-09-06.

[6] Viana F, de la Peña E, Belmonte C (2002). "Specificity of cold thermotransduction is determined by differential ionic channel expression" . Nature Neuroscience . 5 (3): 254–260. doi:10.1038/nn809. PMID 11836533. S2CID 21291629.

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