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Science 14 April 2000:
Vol. 288. no. 5464, pp. 306 - 313
DOI: 10.1126/science.288.5464.306
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Research Articles

Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor

M. J. Caterina, 1* A. Leffler, 3 A. B. Malmberg, 2dagger W. J. Martin, 2ddagger J. Trafton, 2 K. R. Petersen-Zeitz, 2 M. Koltzenburg, 3 A. I. Basbaum, 2 D. Julius 1§

The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43°C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.

1 Department of Cellular and Molecular Pharmacology,
2 Departments of Anatomy and Physiology and the W. M. Keck Center for Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0450, USA.
3 Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
*   Present address: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

dagger    Present address: Neurobiology Unit, Roche Bioscience, Palo Alto, CA 94304-1397, USA.

ddagger    Present address: Merck Research Laboratories, Rahway, NJ 07065, USA.

§   To whom correspondence should be addressed. E-mail: julius{at}socrates.ucsf.edu

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J. Biol. Chem. 282, 26089-26100
   Abstract »    Full Text »    PDF »
Effect of Nicotine on Chorda Tympani Responses to Salty and Sour Stimuli.
V. Lyall, T.-H. T. Phan, S. Mummalaneni, M. Mansouri, G. L. Heck, G. Kobal, and J. A. DeSimone (2007)
J Neurophysiol 98, 1662-1674
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TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice.
B. Zhong and D. H. Wang (2007)
Am J Physiol Heart Circ Physiol 293, H1791-H1798
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Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential.
J. Meng, J. Wang, G. Lawrence, and J. O. Dolly (2007)
J. Cell Sci. 120, 2864-2874
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Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.
A. N. Akopian, N. B. Ruparel, N. A. Jeske, and K. M. Hargreaves (2007)
J. Physiol. 583, 175-193
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4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
M. Trevisani, J. Siemens, S. Materazzi, D. M. Bautista, R. Nassini, B. Campi, N. Imamachi, E. Andre, R. Patacchini, G. S. Cottrell, et al. (2007)
PNAS 104, 13519-13524
   Abstract »    Full Text »    PDF »
Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors.
A. A. Steiner, V. F. Turek, M. C. Almeida, J. J. Burmeister, D. L. Oliveira, J. L. Roberts, A. W. Bannon, M. H. Norman, J.-C. Louis, J. J. S. Treanor, et al. (2007)
J. Neurosci. 27, 7459-7468
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Characterization of SB-705498, a Potent and Selective Vanilloid Receptor-1 (VR1/TRPV1) Antagonist That Inhibits the Capsaicin-, Acid-, and Heat-Mediated Activation of the Receptor.
M. J. Gunthorpe, S. L. Hannan, D. Smart, J. C. Jerman, S. Arpino, G. D. Smith, S. Brough, J. Wright, J. Egerton, S. C. Lappin, et al. (2007)
J. Pharmacol. Exp. Ther. 321, 1183-1192
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Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse.
P. Sikand and L. S. Premkumar (2007)
J. Physiol. 581, 631-647
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Activation Properties of Heterologously Expressed Mammalian TRPV2: EVIDENCE FOR SPECIES DEPENDENCE.
M. P. Neeper, Y. Liu, T. L. Hutchinson, Y. Wang, C. M. Flores, and N. Qin (2007)
J. Biol. Chem. 282, 15894-15902
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Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors.
A. Malkia, R. Madrid, V. Meseguer, E. de la Pena, M. Valero, C. Belmonte, and F. Viana (2007)
J. Physiol. 581, 155-174
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Antinociceptive Pharmacology of N-(4-Chlorobenzyl)-N'-(4-hydroxy-3-iodo-5-methoxybenzyl) Thiourea, a High-Affinity Competitive Antagonist of the Transient Receptor Potential Vanilloid 1 Receptor.
L. Tang, Y. Chen, Z. Chen, P. M. Blumberg, A. P. Kozikowski, and Z. J. Wang (2007)
J. Pharmacol. Exp. Ther. 321, 791-798
   Abstract »    Full Text »    PDF »
Estrogen Amplifies Pain Responses to Uterine Cervical Distension in Rats by Altering Transient Receptor Potential-1 Function.
T. Yan, B. Liu, D. Du, J. C. Eisenach, and C. Tong (2007)
Anesth. Analg. 104, 1246-1250
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Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse.
Z. Helyes, K. Elekes, J. Nemeth, G. Pozsgai, K. Sandor, L. Kereskai, R. Borzsei, E. Pinter, A. Szabo, and J. Szolcsanyi (2007)
Am J Physiol Lung Cell Mol Physiol 292, L1173-L1181
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Downregulation of uncoupling protein-3 in vivo is linked to changes in muscle mitochondrial energy metabolism as a result of capsiate administration.
B. Faraut, B. Giannesini, V. Matarazzo, T. Marqueste, C. Dalmasso, G. Rougon, P. J. Cozzone, and D. Bendahan (2007)
Am J Physiol Endocrinol Metab 292, E1474-E1482
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Hydromineral Neuroendocrinology: Role of TRPV ion channels in sensory transduction of osmotic stimuli in mammals.
W. Liedtke (2007)
Exp Physiol 92, 507-512
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Intensity-Dependent Activation of Extracellular Signal-Regulated Protein Kinase 5 in Sensory Neurons Contributes to Pain Hypersensitivity.
T. Mizushima, K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, T. Mashimo, and K. Noguchi (2007)
J. Pharmacol. Exp. Ther. 321, 28-34
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The Vanilloid Receptor TRPV1 Is Tonically Activated In Vivo and Involved in Body Temperature Regulation.
N. R. Gavva, A. W. Bannon, S. Surapaneni, D. N. Hovland Jr, S. G. Lehto, A. Gore, T. Juan, H. Deng, B. Han, L. Klionsky, et al. (2007)
J. Neurosci. 27, 3366-3374
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