Abstract: Series 101, Lecture 6
The Harvey Lectures Series 101 (2005—2006)
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Lecture #6: Thursday, April 13, 2006 — Time and Location
Pungency and Pain: Understanding the Molecular Mechanisms of Somatosensation
David Julius, PhD
Professor and Vice-Chair
Department of Cellular and Molecular Pharmacology
University of California, San Francisco
San Francisco, California
My group is interested in determining the molecular basis of somatosensation, the process whereby we experience touch and temperature. Our goal is to identify molecules that detect noxious (pain-producing) stimuli and reset the sensitivity of the nervous system following injury. Our approach has been to identify molecular targets for drugs or natural products that mimic psychophysical effects of commonly encountered somatosensory stimuli such as heat or cold. Using this strategy, we have identified two members of the TRP ion channel family, TRPV1 and TRPM8, which are activated by capsaicin and heat, or menthol and cold, respectively. More recently, we have shown that another TRP channel, TRPA1, is targeted by the pungent ingredients in wasabi and garlic. In addition to potential roles in the detection of acute noxious stimuli, each of these channels may also contribute significantly to the mechanisms whereby tissue or nerve injury produces pain hypersensitivity. Insights into signaling pathways that connect injury to channel modulation and neuronal hypersensitivity will be discussed.