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The Journal of Neuroscience, July 14, 2004, 24(28):6410-6415; doi:10.1523/JNEUROSCI.1421-04.2004

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BRIEF COMMUNICATION
Nociceptors Lacking TRPV1 and TRPV2 Have Normal Heat Responses

C. Jeffery Woodbury,1 * Melissa Zwick,2 * Shuying Wang,2 Jeffrey J. Lawson,1 Michael J. Caterina,3 Martin Koltzenburg,4 Kathryn M. Albers,2 H. Richard Koerber,1 and Brian M. Davis2

Departments of 1Neurobiology and 2Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, 3Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and 4University College London, London WC1N 1EH, United Kingdom

Vanilloid receptor 1 (TRPV1) has been proposed to be the principal heat-responsive channel for nociceptive neurons. The skin of both rat and mouse receives major projections from primary sensory afferents that bind the plant lectin isolectin B4 (IB4). The majority of IB4-positive neurons are known to be heat-responsive nociceptors. Previous studies suggested that, unlike rat, mouse IB4-positive cutaneous afferents did not express TRPV1 immunoreactivity. Here, multiple antisera were used to confirm that mouse and rat have different distributions of TRPV1 and that TRPV1 immunoreactivity is absent in heat-sensitive nociceptors. Intracellular recording in TRPV1-/- mice was then used to confirm that TRPV1 was not required for detecting noxious heat. TRPV1-/- mice had more heat-sensitive neurons, and these neurons had normal temperature thresholds and response properties. Moreover, in TRPV1-/- mice, 82% of heat-responsive neurons did not express immunoreactivity for TRPV2, another putative noxious heat channel.

Key words: capsaicin; hypersensitivity; nociception; sensory neurons; skin; pain

Received April 15, 2004; revised May 25, 2004; accepted May 25, 2004.




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