Attenuated fever response in mice lacking TRPV1.
TRPV1, the capsaicin receptor, is expressed not only in nociceptive neurons, but also in other locations, including the hypothalamus. Studies involving systemic or intrahypothalamic capsaicin administration have suggested a role for TRPV1 in body temperature control. To explore this possibility, we examined thermoregulatory responses in TRPV1-/- mice. These mutant animals exhibited no obvious changes in circadian body temperature fluctuation, tolerance to increased (35 degrees C) or decreased (4 degrees C) ambient temperature or ethanol-induced hypothermia. In contrast, fever production in response to the bacterial pyrogen, lipopolysaccharide (LPS) was significantly attenuated in TRPV1-/- mice. Despite this finding, we detected no significant differences between TRPV1-/- and control mice in the extent of LPS-induced c-Fos expression in numerous fever-related brain subregions. These results suggest that TRPV1 participates in the generation of polyphasic fever, perhaps at sites outside the brain.
Iida
Tohko
T
Departments of Biological Chemistry and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Shimizu
Isao
I
Nealen
Michele L
ML
Campbell
Ashley
A
Caterina
Michael
M
D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D005334:Fever / Q000139:chemically induced / Q000235:genetics*; D006358:Hot Temperature; D007473:Ion Channels / Q000172:deficiency*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011749:Pyrogens / Q000494:pharmacology; D050916:TRPV Cation Channels
D007473:Ion Channels; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D011749:Pyrogens; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse