The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

Abstract

Inflammation plays a significant role in the occurrence and development of multiple diseases. This study comprehensively reviews and presents literature from the last five years, showing that acupuncture indeed exerts strong anti-inflammatory effects in multiple biological systems, namely, the immune, digestive, respiratory, nervous, locomotory, circulatory, endocrine, and genitourinary systems. It is well known that localized acupuncture-mediated anti-inflammatory effects involve the regulation of multiple populations and functions of immune cells, including macrophages, granulocytes, mast cells, and T cells. In acupuncture stimulation, macrophages transform from the M1 to the M2 phenotype and the negative TLR4 regulator PPARγ is activated to inhibit the intracellular TLR/MyD88 and NOD signaling pathways. The downstream IκBα/NF-κB and P38 MAPK pathways are subsequently inhibited by acupuncture, followed by suppressed production of inflammasome and proinflammatory mediators. Acupuncture also modulates the balance of helper T cell populations. Furthermore, it inhibits oxidative stress by enhancing SOD activity via the Nrf2/ HO-1 pathway and eliminates the generation of oxygen free radicals, thereby preventing inflammatory cell infiltration. The anti-inflammatory effects of acupuncture on different biological systems are also specific to individual organ microenvironments. As part of its anti-inflammatory action, acupuncture deforms connective tissue and upregulates the secretion of various molecules in acupoints, further activating the NF-κB, MAPK, and ERK pathways in mast cells, fibroblasts, keratinocytes, and monocytes/macrophages. The somatic afferents present in acupuncture-activated acupoints also convey sensory signals to the spinal cord, brainstem, and hypothalamic neurons. Upon information integration in the brain, acupuncture further stimulates multiple neuro-immune pathways, including the cholinergic anti-inflammatory, vagus-adrenal medulla-dopamine, and sympathetic pathways, as well as the hypothalamus-pituitary-adrenal axis, ultimately acting immune cells via the release of crucial neurotransmitters and hormones. This review provides a scientific and reliable basis and viewpoints for the clinical application of acupuncture in various inflammatory conditions.

Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial

“… 19 , 20 , 21 The effects of acupuncture may be achieved through regulating the function of the central nervous system, the cholinergic and the splenic sympathetic anti-inflammatory pathway and the hypothalamic-pituitary-adrenal axis. 13 , 22 , 23 …”

Enhanced Cognition and Neurogenesis in miR-146b Deficient Mice

“…It should be noted that, aside from the novel neuronal functions of miR-146b described in our study, miR-146b is expressed in microglial cells and is involved in the negative regulation of neuroinflammation [25,27]. Previous studies have demonstrated that focal cerebral ischemia and reperfusion can induce inflammation and that acupuncture is able to reduce neuroinflammation [76]. It is possible that acupuncture might improve neurogenesis via expression of anti-inflammatory miR-146b and that inhibition of neurogenesis by the miR-146b inhibition might involve an inflammatory component.…”

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects

“…Macrophages play key roles in the enhancement of pain and can cause peripheral sensitization ( 81 , 82 ). In addition, peripheral sensitization and the prolonged abnormal transmission of pain signals to the dorsal horn of the spinal cord result in increased excitability of neurons at the site of the pain, as well as glial cell activation triggering central sensitization ( 83 – 85 ). The inflammatory response in neural tissue includes immune cell accumulation and cytokine/chemokine release, e.g., paclitaxel directly activates TLR4 and its downstream pathways, leading to an accumulation of macrophages and T cells in neural tissue and the release of large amounts of pro-inflammatory cytokines (TNF-α, IL-17, IL-20, CCL2) via DRG neurons or associated cells by modulating the expression and activity of ion channels in neurons and spinal cord receptors ( 86 ).…”

“…In addition, EA increases vagal nerve activity, suppresses systemic inflammation, and attenuates pancreatic histopathological changes and leukocyte infiltration ( 98 ). In the case of sepsis, the neuroanatomical basis of the EA-driven vagus–adrenal axis is becoming clearer after the Nature Medicine report that EA of the sciatic nerve can lead to dopamine production in the adrenal medulla and can control systemic inflammation through activation of the vagus nerve ( 85 , 99 – 101 ). However, the neuro-immune regulatory mechanisms mediating the acupoint stimulation alleviation of chemotherapy-induced side effects require more investigation.…”