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J. Biol. Chem., Vol. 279, Issue 34, 35133-35138, August 20, 2004

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Warm Temperature-sensitive Transient Receptor Potential Vanilloid 4 (TRPV4) Plays an Essential Role in Thermal Hyperalgesia^*

Hiroshi Todaka, Junichi Taniguchi, Jun-ichi Satoh, Atsuko Mizuno, and Makoto Suzuki

From the Department of Pharmacology, Division of Molecular Pharmacology, Jichi Medical School 3311-1, Yakushiji, Minamikawachi, Tochigi 329-0498, Japan

Animals sense various ranges of temperatures by cutaneous thermal stimuli. Transient receptor potential vanilloid 4 (TRPV4) is a cation channel activated at a warm temperature (over 30 °C) in exogenously expressed cells. We found in the present study that TRPV4 is essential in thermal hyperalgesia at a warm temperature in vivo. TRPV4–/– and TRPV4+/+ mice exhibited the same latency of escape from 35–50 °C hotplates. Neuronal activity in the femoral nerve, however, revealed that the number and activity level of neurons decreased in response to a warm temperature in TRPV4–/– mice. TRPV4–/– mice displayed a significantly longer latency to escape from the plates at 35– 45 °C when hyperalgesia was induced by carrageenan without changes in foot volumes. TRPV4 therefore determines the sensitivity rather than the threshold of painful heat detection and plays an essential role in thermal hyperalgesia.

Received for publication, June 4, 2004

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pharmacology, Division of Molecular Pharmacology, Jichi Medical School 3311-1, Yakushiji, Minamikawachi, Tochigi 329-0498, Japan. Tel.: 81-28-558-7326; Fax: 81-28-544-5541.

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