BACKGROUND: The expression of ubiquitin and energy-associated protein can provoke migraines. Studies have suggested that expression is closely linked to "hyperactivity of liver-yang theory" in Traditional Chinese Medicine (TCM), as well as the function of periphery sympathetic nerve medulla.OBJECTIVE: To observe proteomic changes in a rat migraine model with regard to hyperactivity of liver-yang when treated with Chinese herbs to calm the liver and suppress hyperactive yang compound.DESIGN, TIME AND SETTING: A randomized controlled study. This study was performed at the laboratory of Institute of Integrated Traditional Chinese and Western Medicine, Institute of Human Reproduction and Stem Cell Engineering and Key Laboratory of Cancer Proteomics of Ministry of Health, Xiangya Hospital Affiliated to Central South University between September 2006 and July 2007.MATERIALS: Thirty, male, healthy, Sprague-Dawley rats, aged eight weeks, were included in the final analysis. Aconitc, to calm the liver and suppress hyperactive yang compound, was provided by the Dispensary of Traditional Chinese medicine, Xiangya Hospital, Central South University. A physiological electronic stimulator, type SDQ-1, was provided by Bengbu Practical Institute of Technology. The left trigeminal ganglion was localized and stimulated for 10 minutes, and the rats were orally administered an aconite concoction to establish a rat migraine model with hyperactivity of liver-yang.METHODS: Rats were randomly divided into a normal control group, model group, and TCM treatment group, with 10 rats in each group. The TCM treatment group was orally treated to calm the liver and suppress the hyperactive yang compound once a day for 28 days. In contrast, the model group and normal group were orally administered the same amount of distilled water once a day for 28 days.MAIN OUTCOME MEASURES: The total proteins from adrenal glands of the three groups were separated by two-dimensional gel electrophoresis (2-DE), and 2-DE images were analyzed by PDQuest 7.0 software. Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) was used to obtain peptide mass fingerprints of the differential proteins. Databases were searched to identify the proteins.RESULTS: A total of 30 rats were included in the final analysis. Reproducible 2-DE patterns from rat adrenal gland of the three groups were obtained. Compared with the normal group, nine proteins were down-regulated and five proteins were up-regulated in the model group; however, these expressions returned to normal, or near normal levels, in the TCM treatment group. A total of eight differentially expressed proteins were identified: glycogen phosphorylase, ATP synthase D chain, isovaleryl-CoA dehydrogenase, ubiquitin, Annexin-3, Annexin-A1, Peroxirdoxin-Ⅱ, and heat shock protein-27.CONCLUSION: Liver calming and suppression of the hyperactive yang compound may up-regulate expression of proteins related to energy metabolism and the ubiquitin system. Compounds that are used to treat migraines may contribute to protein functions in the peripheral sympathetic nervous system.