Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation

Electroacupuncture (EA) has been widely applied for illness prevention, treatment or rehabilitation in the clinic, especially for pain management. However, the molecular events that induce these changes remain largely uncharacterized. The periaqueductal gray (PAG) and the spinal dorsal horn (DH) have been verified as two critical regions in the response to EA stimulation in EA analgesia. In this study, a genetic screen was conducted to delineate the gene expression profile in the PAG-DH regions of rats to explore the molecular events of the analgesic effect induced by low-frequency (2-Hz) and high-frequency (100-Hz) EAs. Microarray analysis at two different time points after EA stimulation revealed time-, region- and frequency-specific gene expression changes. These expression differences suggested that modulation of neural-immune interaction in the central nervous system played an important role during EA analgesia. Furthermore, low-frequency EA could regulate gene expression to a greater degree than high-frequency EA. Altogether, the present study offers, for the first time, a characterized transcriptional response pattern in the PAG-DH regions followed by EA stimulation and, thus, provides a solid experimental framework for future in-depth analysis of the mechanisms underlying EA-induced effects.