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Journals The FASEB Journal Volume 21 Issue 13

ABSTRACT Key Words: mouse sensory nerves knockout substance P capsaicin The transient receptor potential vanilloid 1 receptor TRPV1 is a nonselective cation channel (1) best known for its localization on a subset of sensory nerve fibers (C and A ) that release the potent vasoactive peptides substance P and CGRP (2). The chili extract capsaicin and painful heat activate TRPV1, leading to pain and neurogenic inflammation. A growing list of 0892-6638/07/0021-3747 © FASEB proposed endogenous agonists includes protons (3, 4), cannabinoids (5– 8), arachidonate metabolites (e.g., 20-HETE; refs. 9, 10), and other lipoxygenase products (11). It is now realized that common signaling mechanisms can enhance activation of TRPV1—for example, through PKC (12)—thus supporting the concept that TRPV1 can act as an integrator of sensory information (13). There are recent publications of a range of TRPV1 antagonists proposed as drug candidates for novel analgesics and antitussives, but to our knowledge none are appropriate for long-term use in vivo. Furthermore, the traditional method used to probe the role of TRPV1 in vivo, which utilizes neurotoxic doses of capsaicin, affects not only nerves containing TRPV1 receptors but also their contents (14). Thus, in our opinion TRPV1 knockout (TRPV1 KO) mice offer

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