Pain and inflammatory diseases are important clinical indications of acupuncture,which have been widely accepted in the international community.Previous studies have been focusing on rapid analgesia of acupuncture through the regulation of nervous system,but few studies on the inflammation regulatory mechanisms in which acupuncture inhibits the peripheral sensitization-induced pain.Based on studies concerning acupoint mechanisms of acupuncture actions and related researches on acupuncture regulating neuroendocrine and immune systems,we put forward the scientific hypothesis that acupuncture regulates neuroendocrine-immune(NEI)network and key response media therein,so as to achieve anti-inflammatory and analgesic effects in target organs.We have established a platform for acupuncture at ST36 to alleviate inflammatory pain in adjuvant induced arthritic rats.Based on the complex network analysis of multi-dimensional data from multi-time point and multi-site detection of NEI common signaling molecules,we have clarified the regulatory effects of acupuncture on NEI network and corresponding downstream immune network.Results indicated that monocytes/macrophages are the key targeting cells of acupuncture regulation,and acupuncture may display the anti-inflammatory and analgesic effects by regulating polarization of T cells in lymph nodes and polarization of M1/M2 macrophages in inflamed joints/paws.In addition,we have spotted a key molecule for acupuncture analgesia,CXCL1,as well as clarified the novel central analgesic mechanism of acupuncture mediated by CXCL1/CXCR2 desensitization.Thereby,we have provided novel evidence of the anti-inflammatory and analgesic actions of acupuncture through regulating NEI network and several key substances,highlighting a systemic research paradigm for investigating mechanisms of acupuncture actions.