Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor

• Published in: Science (American Association for the Advancement of Science) Vol. 288; no. 5464; pp. 306 - 313
• Main Authors: Caterina, M. J., Leffler, A., Malmberg, A. B., Martin, W. J., Trafton, J., Petersen-Zeitz, K. R., Koltzenburg, M., Basbaum, A. I., Julius, D.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 14.04.2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Biological and medical sciences; Body Temperature - drug effects; Body Weight; Calcium - metabolism; Capsaicin - metabolism; Capsaicin - pharmacology; Cells, Cultured; Diterpenes - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Gene Targeting; Hot Temperature; Hydrogen-Ion Concentration; Inflammation - physiopathology; Mental stimulation; Mice; Mice, Knockout; Mustards; Nerve Fibers - physiology; Neurology; Neurons; Neurons - physiology; Neurons, Afferent - physiology; Nociceptors; Nociceptors - physiology; Pain; Pain - physiopathology; Pain Threshold; Protons; Receptors, Drug - physiology; Rodents; Sensory neurons; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Spinal cord; Spinal Cord - cytology; Spinal Cord - physiology; Stimuli; TRPV Cation Channels; Unmyelinated nerve fibers; vanilloid VR1 receptors; Vertebrates: nervous system and sense organs; Nociception; Vertebrata; Mammalia; Pain; Mouse; Capsaicin; Rodentia; Sensory neuron; Spinal ganglion; Gene expression; In vitro; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.288.5464.306

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.