Acupuncture manipulations are clinically important to traditional Chinese medicine, yet the biological mechanisms have not been fully understood. This study aimed to investigate continuous stimulation-induced gene expression changes at stimulated and non-stimulated adjacent acupoints in the same meridian. Catgut embedding into acupoint (CEP) was conducted at acupoint Yanglingquan (gall bladder meridian of foot-shaoyang 34, GB34) of Sprague Dawley rats once or continuously for eight weeks, and gene expression changes at GB34 were assessed by gene chip array analysis 72 h after the last CEP treatment. A total of 688 genes exhibited opposite changes in expression between the two treatments, and 1,336 genes were regulated only by the eight-week CEP treatment. Ingenuity Pathway Analysis revealed that among these differentially regulated genes by one-time and eight-week CEP treatment, insulin-like growth factor-1 pathway and integrin-linked kinase pathway, and Wnt/~ catenin signaling pathway match the observed gene changes to predicted up/down regulation patterns. Upstream analysis further predicted six molecules, namely, tumor necrosis factor, interleukin 1~, interleukin la, kallikrein-related peptidase 5, protein kinase Ca, and catenin ~1. On the other hand, continuous eight-week CEP stimulation at acupoint Xuanzhong (GB39) caused similar changes in the expression of 32 genes at acupoints GB34 and Fengshi (GB31) on the same meridian. Taken together, our results provide the first molecular evidence for the local acupoints' mechanisms for acupoint sensitization theory, and implicate the existence of signaling pathways, either direct or indirect, between acupoints within the meridian GB.
