Our previous results indicated that dynorphin in the spinal dorsal horn mediates the analgesic effect of high frequency electroacupuncture stimulation (EAS). Here we report that the transcriptional repressor downstream regulatory element antagonist modulator (DREAM) of dynorphin precursor-preprodynorphin (PPD) may participate in this process. In normal rats, 100 Hz, but not 2 Hz EAS triggered the nuclear export and membrane translocation of DREAM concomitantly with the upregulation of PPD mRNA in the dorsal horn. In inflammatory rats, both 2 and 100 Hz EAS alleviated thermal and mechanical hypersensitivity and caused the nuclear export and membrane translocation of DREAM, but only 100 Hz EAS enhanced the mRNA level of PPD and DREAM. These results suggest the role of DREAM in the dorsal horn in the regulation of PPD gene expression by EAS is frequency dependent, and DREAM may exert different roles in different frequency EAS under physiological and inflammatory conditions.