Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Feb;165(4):787-801.
doi: 10.1111/j.1476-5381.2011.01601.x.

The thermo-TRP ion channel family: properties and therapeutic implications

Affiliations
Review

The thermo-TRP ion channel family: properties and therapeutic implications

Laura Vay et al. Br J Pharmacol. 2012 Feb.

Abstract

The thermo-transient receptor potentials (TRPs), a recently discovered family of ion channels activated by temperature, are expressed in primary sensory nerve terminals where they provide information about thermal changes in the environment. Six thermo-TRPs have been characterised to date: TRP vanilloid (TRPV) 1 and 2 are activated by painful levels of heat, TRPV3 and 4 respond to non-painful warmth, TRP melastatin 8 is activated by non-painful cool temperatures, while TRP ankyrin (TRPA) 1 is activated by painful cold. The thermal thresholds of many thermo-TRPs are known to be modulated by extracellular mediators, released by tissue damage or inflammation, such as bradykinin, PG and growth factors. There have been intensive efforts recently to develop antagonists of thermo-TRP channels, particularly of the noxious thermal sensors TRPV1 and TRPA1. Blockers of these channels are likely to have therapeutic uses as novel analgesics, but may also cause unacceptable side effects. Controlling the modulation of thermo-TRPs by inflammatory mediators may be a useful alternative strategy in developing novel analgesics.

PubMed Disclaimer

Figures

Figure 1
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- terminals (NB: not drawn to scale). All thermo-TRPs have a variable number of ankyrin repeat domains in the N-terminus (except TRPM8, which has none). Thermo-TRPs display distinct thermal thresholds from very hot (TRPV2) to cold (TRPA1). Each thermo-TRP is also activated by specific natural compounds and by synthetic substances, which are also known to induce the relevant thermal and pain sensations in humans. This figure provides a schematic overview of some of the main agonists – see Table 1 for a more complete list. BAA, bisandrographolide A.

Similar articles

Cited by

References

    1. Airaksinen MS, Titievsky A, Saarma M. GDNF family neurotrophic factor signaling: four masters, one servant? Mol Cell Neurosci. 1999;13:313–325. - PubMed
    1. Albers KM, Woodbury CJ, Ritter AM, Davis BM, Koerber HR. Glial cell-line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors. J Neurosci. 2006;26:2981–2990. - PMC - PubMed
    1. Alessandri-Haber N, Joseph E, Dina OA, Liedtke W, Levine JD. TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediator. Pain. 2005;118:70–79. - PubMed
    1. Babes A, Zorzon D, Reid G. Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor. Eur J Neurosci. 2004;20:2276–2282. - PubMed
    1. Babes A, Zorzon D, Reid G. A novel type of cold-sensitive neuron in rat dorsal root ganglia with rapid adaptation to cooling stimuli. Eur J Neurosci. 2006;24:691–698. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources