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Peripheral thermosensation in mammals

Nature Reviews Neuroscience volume 15, pages 573–589 (2014)Cite this article

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Key Points

  • The somatosensory system contains temperature-sensitive primary sensory neurons that convey thermal information from the skin and peripheral organs to the CNS. This sensory input enables the avoidance of prolonged contact with dangerously hot or cold objects and helps to maintain a core body temperature of ∼37 °C with minimal energy expenditure.

  • Thermal stimuli are coded by the action potential firing patterns of different types of temperature-sensitive primary sensory neurons, the cell bodies of which are located in the dorsal root and trigeminal ganglia.

  • The generation of action potentials in sensory nerve endings in response to a thermal stimulation depends on the activity of an array of temperature-sensitive ion channels. Members of the transient receptor potential (TRP) cation channel family of ion channels have been proposed as the prime thermosensors, but more recent research suggests additional important contributions from other ion channel types.

  • Several key temperature-sensitive ion channels exhibit intrinsic thermosensitivity, which implies substantial differences in enthalpy and entropy between the closed and open conformation of the channel proteins. The structural basis of this process is currently unclear.

  • Dysregulation of temperature-sensitive ion channels in sensory neurons can lead to thermal hypersensitivity and chronic pain, making these channels attractive targets for novel analgesic therapies.

  • Pharmacological inhibition of the prototype heat sensor TRPV1 and the cold sensor TRPM8 directly affects core body temperature, illustrating the important influence of peripheral thermosensation on thermoregulatory responses. Preventing unwanted changes in core body temperature is an important challenge in the future development of therapies that target temperature-sensitive ion channels.

Abstract

Our ability to perceive temperature is crucial: it enables us to swiftly react to noxiously cold or hot objects and helps us to maintain a constant body temperature. Sensory nerve endings, upon depolarization by temperature-gated ion channels, convey electrical signals from the periphery to the CNS, eliciting a sense of temperature. In the past two decades, we have witnessed important advances in our understanding of mammalian thermosensation, with the identification and animal-model assessment of candidate molecular thermosensors — such as types of transient receptor potential (TRP) cation channels — involved in peripheral thermosensation. Ongoing research aims to understand how these miniature thermometers operate at the cellular and molecular level, and how they can be pharmacologically targeted to treat pain without disturbing vital thermoregulatory processes.

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Figure 1: Neurons involved in thermosensation.
Figure 2: Temperature dependence of ion channels involved in thermosensation.
Figure 3: Potential mechanisms underlying temperature-sensitive gating of ion channels.
Figure 4: Putative regions implicated in the heat sensitivity of TRPV channels.

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Acknowledgements

The authors thank all members of the Laboratory of Ion Channel Research for helpful discussions. This work was supported by grants from the Belgian Science Policy (IUAP P7/13 to T.V.), the Research Foundation - Flanders (G.0825.11 to T.V. and J.V.), the Research Council of the KU Leuven (PF-TRPLe to T.V.) and the Planckaert-De Waele fund (to J.V.).

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Authors and Affiliations

  1. Laboratory of Experimental Gynaecology, KU Leuven, Herestraat 49 BOX 611, Leuven, B-3000, Belgium

    Joris Vriens

  2. Laboratory of Ion Channel Research and TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49 BOX 802, Leuven, B-3000, Belgium

    Bernd Nilius & Thomas Voets

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  1. Joris Vriens
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  2. Bernd Nilius
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Correspondence to Thomas Voets.

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Glossary

Transient receptor potential channels

(TRP channels). A family of cation channels homologous to the product of the Drosophila melanogaster trp gene. Several mammalian members of this family function as molecular thermosensors.

Aδ fibres

Sensory neurons with medium-diameter, thinly myelinated axons and a medium conduction velocity of between 2 and 30 metres per second.

C fibres

Sensory neurons with small-diameter, non-myelinated axons and a low conduction velocity of between 0.5 and 2 metres per second.

Adaptation

The reduction over time of the response of a neuron to a constant sensory stimulus.

Q10 value

A dimensionless value to quantify the temperature dependence of a process. It is defined as the ratio between reaction rates or current amplitudes measured at two temperatures 10 degrees apart.

Hyperalgesia

Increased sensitivity to a painful stimulus.

Tetrodotoxin

(TTX). A toxin from puffer fish that potently blocks several types of voltage-gated Na+ channels.

Enthalpy

A thermodynamic measure of the internal energy of a system. In a protein, formation of stabilizing intramolecular bonds causes a reduction in enthalpy.

Entropy

A thermodynamic measure of the disorder of a system. It is determined by the number of different configurations (microstates) that correspond to a specific macrostate.

Allodynia

Pain in response to a stimulus that does not normally evoke pain.

Complete Freund's adjuvant

(CFA). An emulsion of inactivated and dried mycobacteria. When injected subcutaneously, it induces local inflammation and hypersensitivity to thermal and mechanical stimuli.

Carrageenan

A sulphated polysaccharide extracted from red edible seaweeds. When injected subcutaneously, it induces local inflammation and hypersensitivity to thermal and mechanical stimuli.

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Vriens, J., Nilius, B. & Voets, T. Peripheral thermosensation in mammals. Nat Rev Neurosci 15, 573–589 (2014). https://doi.org/10.1038/nrn3784

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