The neuro-immune microenvironment of acupoints—initiation of acupuncture effectiveness

Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF-κB, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca²⁺ influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro-immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future.