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PLOS ONE  2014 

Acute Heat-Evoked Temperature Sensation Is Impaired but Not Abolished in Mice Lacking TRPV1 and TRPV3 Channels

DOI: 10.1371/journal.pone.0099828

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Abstract:

The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.

References

[1]  Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, et al. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389: 816–824.
[2]  Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87: 165–217.
[3]  Dhaka A, Viswanath V, Patapoutian A (2006) Trp ion channels and temperature sensation. Annual review of neuroscience 29: 135–161.
[4]  Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4: 529–539.
[5]  Patapoutian A (2005) TRP Channels and Thermosensation. Chem Senses 30 Suppl 1i193–i194.
[6]  Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, et al. (2002) A heat-sensitive TRP channel expressed in keratinocytes. Science 296: 2046–2049.
[7]  Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, et al. (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418: 181–186.
[8]  Chung MK, Lee H, Caterina MJ (2003) Warm temperatures activate TRPV4 in mouse 308 keratinocytes. J Biol Chem 278: 32037–32046.
[9]  Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ (2004) TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. J Biol Chem 279: 21569–21575.
[10]  Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398: 436–441.
[11]  Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, et al. (2005) Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307: 1468–1472.
[12]  Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, et al. (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288: 306–313.
[13]  Park U, Vastani N, Guan Y, Raja SN, Koltzenburg M, et al. (2011) TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J Neurosci 31: 11425–11436.
[14]  Lee H, Iida T, Mizuno A, Suzuki M, Caterina MJ (2005) Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4. J Neurosci 25: 1304–1310.
[15]  Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, et al. (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405: 183–187.
[16]  Christoph T, Bahrenberg G, De Vry J, Englberger W, Erdmann VA, et al. (2008) Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice. Mol Cell Neurosci 37: 579–589.
[17]  Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, et al. (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418: 186–190.
[18]  Huang SM, Li X, Yu Y, Wang J, Caterina MJ (2011) TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation. Mol Pain 7: 37.
[19]  Todaka H, Taniguchi J, Satoh J, Mizuno A, Suzuki M (2004) Warm temperature-sensitive transient receptor potential vanilloid 4 (TRPV4) plays an essential role in thermal hyperalgesia. J Biol Chem 279: 35133–35138.
[20]  Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53: 55–63.
[21]  Yalcin I, Charlet A, Freund-Mercier MJ, Barrot M, Poisbeau P (2009) Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. J Pain 10: 767–773.
[22]  Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, et al. (2008) Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136: 202–210.
[23]  Romanovsky AA, Almeida MC, Garami A, Steiner AA, Norman MH, et al. (2009) The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not. Pharmacol Rev 61: 228–261.
[24]  Schicho R, Florian W, Liebmann I, Holzer P, Lippe IT (2004) Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa. Eur J Neurosci 19: 1811–1818.
[25]  Szallasi A, Nilsson S, Farkas-Szallasi T, Blumberg PM, Hokfelt T, et al. (1995) Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 703: 175–183.
[26]  Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, et al. (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21: 531–543.
[27]  Cavanaugh DJ, Chesler AT, Braz JM, Shah NM, Julius D, et al. (2011) Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J Neurosci 31: 10119–10127.
[28]  Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, et al. (2011) Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci 31: 5067–5077.
[29]  Iida T, Shimizu I, Nealen ML, Campbell A, Caterina M (2005) Attenuated fever response in mice lacking TRPV1. Neurosci Lett 378: 28–33.
[30]  Szelenyi Z, Hummel Z, Szolcsanyi J, Davis JB (2004) Daily body temperature rhythm and heat tolerance in TRPV1 knockout and capsaicin pretreated mice. Eur J Neurosci 19: 1421–1424.
[31]  Toth DM, Szoke E, Bolcskei K, Kvell K, Bender B, et al. (2011) Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cellular and molecular life sciences : CMLS 68: 2589–2601.
[32]  Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, et al. (2011) Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J Neurosci 31: 1721–1733.
[33]  Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, et al. (2007) Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci 27: 7459–7468.
[34]  Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, et al. (2007) The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci 27: 3366–3374.
[35]  Tamayo N, Liao H, Stec MM, Wang X, Chakrabarti P, et al. (2008) Design and synthesis of peripherally restricted transient receptor potential vanilloid 1 (TRPV1) antagonists. J Med Chem 51: 2744–2757.
[36]  Miyamoto T, Petrus MJ, Dubin AE, Patapoutian A (2011) TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin. Nat Commun 2: 369.
[37]  Miyamoto T, Dubin AE, Petrus MJ, Patapoutian A (2009) TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLoS One 4: e7596.
[38]  Huang SM, Lee H, Chung MK, Park U, Yu YY, et al. (2008) Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. J Neurosci 28: 13727–13737.
[39]  Kunkler PE, Ballard CJ, Oxford GS, Hurley JH (2011) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain 152: 38–44.
[40]  Marsch R, Foeller E, Rammes G, Bunck M, Kossl M, et al. (2007) Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice. J Neurosci 27: 832–839.

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