A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis

Liu, Shenbin; Wang, Zhifu; Su, Yang-Shuai; Qi, Lu; Yang, Wei; Fu, Mingzhou; Jing, Xiang-Hong; Wang, Yan-Qing; Ma, Qiufu

doi:10.1038/s41586-021-04001-4

Cited by 309 publications

(184 citation statements)

References 32 publications

Supporting

Mentioning

176

Contrasting

Unclassified

Order By: Relevance

“…In contrast, spinal sympathetic reflexes, which are independent of the PROKR2ADV neurons, can be evoked by high-intensity EA at both ST25 and ST36 acupoints. 152 The Sympathetic Pathway Sympathetic nerves play dual roles in the regulation of inflammatory responses, mediating both pro-and antiinflammatory effects. 153 It is reported that sympathetic tyrosine hydroxylase immunoreactive (TH-IR) fibers form "basket-like" structures around the coloninnervating DRG neurons following colonic inflammation and contribute to the inflammatory visceral pain and somatic hyperalgesia.…”

Section: Dovepressmentioning

confidence: 99%

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

Li¹,

Guo²,

Gong³

et al. 2021

JIR

View full text Add to dashboard Cite

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.

show abstract

Section: Dovepressmentioning

confidence: 99%

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

Li¹,

Guo²,

Gong³

et al. 2021

JIR

View full text Add to dashboard Cite

show abstract

“…The role of acupoints is demonstrated by the fact that in rats and dogs, acupoint vaccination induced a higher antibody response than in other anatomical sites [31]. Recent studies further provide a neuroanatomical basis for the selectivity and speci city of acupoints in driving the vagal-adrenal anti-in ammatory axis [32]. In this study, we also provide the experimental evidence for the presence of acupoint selectivity (for example, ST36 and IL11 versus non-effective traditional nonacupoint in 5 mm above ST36 and at the midpoint of the acromial part of the deltoid muscle) and the injectant selectivity (for example, autologous whole blood versus normal saline) in regulating Th1/Th2 immune responses.…”

Section: Discussionmentioning

confidence: 98%

Acupoint Autohemotherapy Attenuates DNCB-induced Atopic Dermatitis Lesions by Regulating Th1/Th2 Cytokine Balance in BALB/c Mice

Zeng¹,

Huang²,

Chen³

et al. 2021

Preprint

View full text Add to dashboard Cite

Objective Acupoint autohemotherapy (A-AHT) is considered an effective therapy for atopic dermatitis (AD) with few side-effects. Previous experiments showed the treatment had the potential to regulate T helper (Th) 1 and Th2 cytokines, like interferon (IFN)- gamma and interleukin (IL)- 4. This study focuses on the effects of A-AHT on the AD-like skin lesions through regulating Th1/Th2 immune responses. Methods The treatments of A-AHT, sham acupoint autohemotherapy and acupoint injection of normal saline were administered in the AD mice once every other day for 4 weeks. The total immunoglobulin (Ig) E, IL-4 and IFN-γ cytokine levels in the serum were examined after animal sacrifice. Th1/Th2 expression was analyzed in murine spleen cells via flow cytometry and immunohistochemical analysis of GATA-3 and T-bet in skin lesions were further assessed. Results Either type of repeated autologous whole blood (AWB) injection (into acupoint or sham acupoint) reduced the severity of AD-like symptoms and level of serum IgE. All of the three treatments had the similar inhibitory effect on levels of IL-4 and upregulation on the ratio of IFN-γ/IL-4, while differed on Th1/Th2 ratio as A-AHT regulates the body’s Th1/Th2 shift. This treatment also increased the related transcription factors T-bet expression, and upregulated T-bet/GATA3 ratio compared with the DNCB group. These differences were significant only in A-AHT group. Conclusion A-AHT effectively reduces AD symptoms and serum IgE levels in a mouse model and may act by regulating Th1/Th2 immune responses.

show abstract

“…Therapeutic results in preclinical studies using vagus nerve stimulation, choline esterase inhibitors, or α7-nicotinic acetylcholine receptor (α7nAChR) agonists are strikingly similar to those seen after HMGB1-specific blocking treatment regarding kinetics and final outcome [ 3 , 111 , 112 , 113 , 114 ]. Acetylcholine inhibits HMGB1 release [ 102 , 103 , 105 , 106 , 107 , 115 , 116 , 117 ], TLR4/MyD88/NF-κB signaling [ 118 ], and RAGE-mediated endocytosis of HMGB1 and HMGB1 complex-bound to DAMPs or PAMPs [ 60 ]. Each one of these inhibitory accomplishments is beneficial for controlling HMGB1-mediated inflammation.…”

Section: Hmgb1 and Acetylcholine-potent Antagonists Balancing Inflammationmentioning

confidence: 99%

“…Furthermore, electroacupuncture pretreatment using a specific acupoint termed ST36 attenuated acute lung injury through α7nAChR-mediated inhibition of HMGB1 release in rats after cardiopulmonary bypass [ 107 ]. It was recently demonstrated that low-intensity electroacupuncture stimulation of the ST36 acupoint excited PROKR2-expressing sensory neurons to activate the cholinergic anti-inflammatory system [ 116 ].…”

Section: Hmgb1 and Acetylcholine-potent Antagonists Balancing Inflammationmentioning

confidence: 99%

Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation

Andersson

Tracey

Yang

2021

Cells

View full text Add to dashboard Cite

High mobility group box 1 protein (HMGB1), a highly conserved nuclear DNA-binding protein, is a “damage-associated molecular pattern” molecule (DAMP) implicated in both stimulating and inhibiting innate immunity. As reviewed here, HMGB1 is an oxidation-reduction sensitive DAMP bearing three cysteines, and the post-translational modification of these residues establishes its proinflammatory and anti-inflammatory activities by binding to different extracellular cell surface receptors. The redox-sensitive signaling mechanisms of HMGB1 also occupy an important niche in innate immunity because HMGB1 may carry other DAMPs and pathogen-associated molecular pattern molecules (PAMPs). HMGB1 with DAMP/PAMP cofactors bind to the receptor for advanced glycation end products (RAGE) which internalizes the HMGB1 complexes by endocytosis for incorporation in lysosomal compartments. Intra-lysosomal HMGB1 disrupts lysosomal membranes thereby releasing the HMGB1-transported molecules to stimulate cytosolic sensors that mediate inflammation. This HMGB1-DAMP/PAMP cofactor pathway slowed the development of HMGB1-binding antagonists for diagnostic or therapeutic use. However, recent discoveries that HMGB1 released from neurons mediates inflammation via the TLR4 receptor system, and that cancer cells express fully oxidized HMGB1 as an immunosuppressive mechanism, offer new paths to targeting HMGB1 for inflammation, pain, and cancer.

show abstract

A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis

Cited by 309 publications

References 32 publications

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

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

Acupoint Autohemotherapy Attenuates DNCB-induced Atopic Dermatitis Lesions by Regulating Th1/Th2 Cytokine Balance in BALB/c Mice

Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation

Contact Info

Product

Resources

About