The daily fluctuations of many physiologic and behavioral parameters are differentially influenced by either central or peripheral clocks in mammals. Since substance P (SP) oscillates in some brain tissues and plays an indispensable role in modulating inflammatory pain at the spinal level, we speculated that SP mediates circadian nociception transmission at the spinal level. Methods: In the present study behavioral observation, realtime polymerase chain reaction, luciferase assay, chromatin

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... noprecipitation, and immunohistochemistry stain methods were used to investigate the role of SP in the spinal circadian nociception transmission and its regulation mechanism. Results: Our results showed that under transcriptional regulation of BMAL1:CLOCK heterodimers, SP's coding gene Tac1 expression oscillates in dorsal root ganglion (n ϭ 36), but not in the spinal dorsal horn. Further, the expression of