Mechanism of electroacupuncture on inflammatory pain: neural-im- mune-endocrine interactions

Nociceptive signals are transmitted by peripheral afferents to the central nervous system under pain condition, a process that involves various neurotransmitters and pathways. Electroacupuncture (EA) has been widely used as a pain management technique in clinical practice. Emerging studies have shown that EA can inhibit the induction and transmission of pain signals and, consequently, mediate anti-nociceptive and anti-inflammatory effects by rebalancing the neural-immune-endocrine interactions. This review summarizes the neural-immune-endocrine circuit including peripheral afferent and central efferent, contributing to EA-induced neuroimmune and neuroendocrine modulation in inflammatory pain models. The peripheral afferent circuit includes crosstalk among immune cells, inflammatory cytokines, peripheral nociceptors. In central efferent primarily involves the neuroinflammatory interactions between spinal nociceptive neurons and glial cells. Furthermore, the hypothalamic-pituitary-adrenal axis, sympathetic and vagal nervous may serve as an essential pathway involved in the mechanism of acupuncture-mediated analgesia within the interactions of the central, immune and endocrine systems. Overall, this review focuses on the interactions of neural-immune-endocrine in inflammatory pain, which may be underlying the mechanism of EA-induced anti-inflammatory and antinociceptive effect.