Detection of temperature, both of the surroundings and of the body itself, is critical for maintaining normal physiological functioning. To date, a number of thermo‐sensitive ion channels have been reported to be involved in thermosensation, six of which belong to the transient receptor potential (TRP) superfamily of nonselective cation channels. Each of these operates over a distinct temperature range and many respond to natural compounds that elicit sensations of heat or cold. The best studied is TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin, the active principle of chilli peppers, and a painful heat receptor which responds to temperatures over 42°C. Our understanding of cold transduction has also rapidly increased in recent years with the intriguing discovery of the cold receptors TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1).

Key concepts

  • Our current understanding of thermosensation comes mainly from the identification of six temperature‐sensitive ion channels (thermo‐TRP channels) belonging to the transient receptor potential (TRP) superfamily of nonselective calcium channels.

  • Each thermo‐TRP operates over a distinct temperature range. Four of them (TRPV1–4) are activated by heat, and two of them (TRPM8 and TRPA1) are activated by cold.

  • Thermo‐TRPs also respond to natural compounds that elicit corresponding psychophysical sensations of heat or cold.

  • The response of these channels is regulated after tissue damage and is subjected to modulation by inflammatory mediators released at the site of injury. The altered sensitivity of these channels accounts for the phenomenon of thermal hyperalgesia.

  • Inflammatory mediators sensitize TRPV1 via the activation of protein kinases such as protein kinase C (PKC), protein kinase A (PKA) and Src. The modulation of TRPV1 by PKC and PKA depends on the correct positioning of the kinases by a scaffolding protein, AKAP79/150.

  • There are other possible mechanisms involved in thermosensation, for example, modulation of potassium channels such as TREK‐2.

Keywords: TRP channels; sensory neurons; temperature; inflammation; pain

Figure 1.

Schematic depiction of the six mammalian thermo‐TRP channels. Each subunit consists of six transmembrane domains (S1–S6), a hydrophobic pore loop linking transmembrane segments five (S5) and six (S6), and large cytoplasmic N‐ and C‐termini. All thermo‐TRPs except TRPM8 have a variable number of ankyrin repeat domains in the N‐terminus. All of the thermo‐TRPs display distinct thermal thresholds from very hot (TRPV2) to cold (TRPA1). Each thermo‐TRP is also activated by specific natural compounds and synthetic substances, which are also known to induce the relevant thermal and pain sensations in humans.

Figure 2.

Signalling pathways involved in the sensitization of TRPV1 by serine‐threonine phosphorylation. Inflammatory mediators released during injury induce hyperalgesia by enhancing the activation of the heat and capsaicin gated ion channel, TRPV1, in response to thermal and other stimuli. TRPV1 plays a critical role in the development of thermal hyperalgesia induced by these mediators. Prostaglandin E2, bradykinin, ATP, proteinases and tachykinins bind to their specific G protein‐coupled receptors, resulting in the activation of multiple second messenger pathways that have important role in sensitization. Recently, modulation of TRPV1 by PKC, PKA and the phosphatase calcineurin has been reported to depend on the formation of a signalling complex involving these enzymes, the scaffolding protein AKAP79/150 and TRPV1 (shown at top) (Zhang et al., ).

Figure 3.

Schematic diagram of the signalling pathways important in sensitization of TRPV1 by TrkA. The functionally most significant pathway is shown at the left (yellow, solid arrows). A smaller component of sensitization following exposure to NGF is mediated by phosphorylation of TRPV1 at residues S502 and S801, probably by the PLCβ/PKCε pathway (green, dashed arrows). PKCε is a crucial intermediate in sensitization of TRPV1 by bradykinin (pathway shown at the lower right of the diagram) (Zhang et al., ).



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Further Reading

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Story GM (2006) The emerging role of TRP channels in mechanisms of temperature and pain sensation. Current Neuropharmacology 4: 183–196.

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Mak, Stephanie, Zhang, Xuming, and McNaughton, Peter(Sep 2009) Thermosensation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021394]