CLOCK regulates the circadian rhythm of kaolin-induced writhing behavior in mice.
Kaolin-induced writhing reaction is a simple and convenient model of bradykinin-induced pain for assessment of analgesic actions. In this study, we demonstrated that the number of kaolin-induced writhing reaction was fluctuated in a circadian manner that peaked at the end of the resting period (dusk) and reduced during the active (dark) period in mice. Circadian rhythm of the writhing intensity was completely phase-shifted by a time-imposed restricted feeding. On the other hand, 24 h of food deprivation did not affect the writhing intensity, suggesting that the endogenous clock that can be entrained to the scheduled feeding is responsible to the circadian intensity of the writhing reaction. Day/night fluctuation of the writhing intensity was completely abolished and the writhing reaction was significantly reduced in the circadian clock deficient Clock-mutant mice, although the kaolin-induced bradykinin production and blood pressure suppression were not affected in these mutant mice. Our present study suggested that the circadian variation of the pain sensitivity is governed by the food-entrainable endogenous clock and by the circadian clock molecules in mammals.
Oishi
Katsutaka
K
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Ohkura
Naoki
N
Sei
Hiroyoshi
H
Matsuda
Juzo
J
Ishida
Norio
N
D000818:Animals; D000930:Antidiarrheals; D001069:Appetite Regulation / Q000502:physiology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D007616:Kaolin; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008818:Mice, Neurologic Mutants; D009154:Mutation / Q000235:genetics; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D000930:Antidiarrheals; D015534:Trans-Activators; D007616:Kaolin; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D001920:Bradykinin