Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia—Nuclear Factor κB Signaling Pathway

Zhang, Kuo; Zhao, Xue; Yang, Tao; Zhang, Yanfang; Yan, Ya-Wen; Xu, Zhifang; Gong, Yi-Nan; Liu, Yangyang; Guo, Yongming; Guo, Yi

doi:10.1007/s11655-020-3435-6

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…Alternately, NF-κB inhibitors suppress the acupuncture analgesic effect by reducing IL-6 levels and the proportion of CD68 + macrophages. 116 In addition, the association of adenosine to adenylate A1 receptors in acupoints mediates the anti-inflammatory and analgesic effects of acupuncture in CFA models. 117 , 118 It is also reported that EA at ST36 for 7 days increases CB2R expression, with no effect on CB1R in the acupoint, thereby inhibiting the influx of calcium ions, suppressing the TLR4/NF-κB pathway in the spleen, and eventually, down-regulating expressions of TNF-α, IL-1β, and IL-6 in the serum, 119 suggesting that the cannabinoid system in acupoints is intricately involved in the acupuncture-mediated anti-inflammatory process.…”

Section: Discussionmentioning

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

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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.

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Section: Discussionmentioning

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

Self Cite

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“…Acupuncture is a type of benign microinvasive stimulation that involves inserting acupoints and inducing the deformation of local connective tissues, leading to release of various chemical substances, such as interleukins, chemokines, tumor necrosis factors, adenosine triphosphate (ATP) and high migration molecules ( Goldman et al, 2010 ; Zhang et al, 2018 ). These molecules are secreted into the extracellular space and bind their corresponding receptors, which results in the recruitment of mast cells, fibroblasts, neutrophils, and monocytes/macrophages, thereby promoting signal cascade amplification of acupuncture and activating the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK), and other signaling pathways in cells ( Park et al, 2014 ; Zhang et al, 2021 ). These effects enhance intercellular communication as well as information transmission, and improve network connectivity of local microenvironments of acupoints ( Wu et al, 2015 ).…”

Section: The Role and Rule Of Afferent Fibers In Signal Initiation An...mentioning

confidence: 99%

Effects and mechanisms of acupuncture analgesia mediated by afferent nerves in acupoint microenvironments

Fan,

Dou,

Wang

et al. 2024

Front. Neurosci.

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In the past few decades, the use of acupuncture analgesia in clinical practice has increased worldwide. This is due to its various benefits, including natural alleviation of pain without causing various adverse effects associated with non-steroidal anti-inflammatory drugs (NSAID) and opioids. The acupoint represents the initial site of acupuncture stimulation, where diverse types of nerve fibers located at the acupoint hold significant roles in the generation and transmission of acupuncture-related information. In this study, we analyzed the patterns and mechanisms of acupuncture analgesic mediated by acupoint afferent fibers, and found that acupuncture stimulates acupoints which rapidly and directly induces activation of high-density primary afferent fibers under the acupoints, including myelinated A fibers and unmyelinated C fibers. During acupuncture stimulation at the muscle layer, the analgesic effects can be induced by stimulation of A fiber threshold intensity. At the skin layer, the analgesic effects can only be produced by stimulation of C fiber threshold intensity. Electroacupuncture (EA) activates A fibers, while manual acupuncture (MA) activates both A and C fibers. Furthermore, acupuncture alters acupoint microenvironments, which positively modulates afferent fibers, enhancing the transmission of analgesic signals. In addition to local activation and conduction at acupoints, nerve fibers mediate the transmission of acupuncture information to pain centers. In the spinal cord, acupuncture activates neurons by inducing afferent fiber depolarization, modulating pain gating, inhibiting long-term potentiation (LTP) of the spinal dorsal horn and wide dynamic range (WDR) neuronal activities. At higher nerve centers, acupuncture inhibits neuronal activation in pain-related brain regions. In summary, acupuncture inhibits pain signal transmission at peripheral and central systems by activating different patterns of afferent fibers located on various layers of acupoints. This study provides ideas for enhancing the precise application and clinical translation of acupuncture.

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“…Nuclear factor kappa-B (NF- κ B) is an important nuclear transcription factor in cells involved in inflammation, immunity, pain, and stress responses [ 10 ]. NF- κ B signaling and gene expression of its cytokines have been associated with acupuncture points [ 11 ]. In addition, it has reported that the analgesic effects of acupuncture can be attenuated by reducing IL-6 levels and the proportion of CD68 macrophages via using NF- κ B inhibitors [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Electroacupuncture on Gastrointestinal Motility Function, Pain, and Inflammation via Transient Receptor Potential Vanilloid 1 in a Rat Model after Colonic Anastomoses

et al. 2022

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Background. Complications after colon surgery are a major obstacle to postoperative recovery. The purpose of this study was to investigate the effect of electroacupuncture (EA) at Zusanli (ST36) on gastrointestinal motility in rats after colonic anastomosis and the mechanism of transient receptor potential vanillin 1 (TRPV1) channel in regulating gastrointestinal motility, pain, and inflammation. Methods. The rats were randomly divided into six groups, including the control, model, EA, sham-EA, capsaicin, and capsaicin+EA groups, with preoperative capsaicin pretreatment and EA treatment at ST36 acupoint after surgery. Rats were treated using EA at ST36 or sham acupoints after surgery for 5 days. Capsaicin was intraperitoneally injected into rats 3 hours before surgery. Gastrointestinal motility was assessed by measuring the gastric residue, small intestinal propulsion in vivo, contractile tension, and frequency of isolated muscle strips in vitro. The mechanical withdrawal threshold (MWT) of abdominal incision skin and spontaneous nociceptive scores were observed and recorded in rats after colon anastomosis. The expressions of TRPV1, substance P (SP), neurokinin 1 (NK1) receptor, nuclear factor kappa-B (NF-κB), interleukin- (IL-) 6, L-1β, and tumor necrosis factor- (TNF-) α were determined. Results. Compared with the model group, electroacupuncture at ST36 point could significantly reduce the residual rate of stomach in rats after operation and increase the propulsive force of the small intestine and the contraction tension of the isolated smooth muscle. Electroacupuncture also increased postoperative day 3 MWT values and decreased postoperative spontaneous nociception scores. In addition, electroacupuncture treatment downregulated the expressions of IL-6, IL-1β, TNF-α, TRPV1, NF-κB, SP, and NK1 receptors in the colon tissue of rats after colonic anastomosis. Conclusions. Our study showed that electroacupuncture at ST36 acupoint could improve gastrointestinal motility in rats after colonic anastomosis and relieve intestinal inflammation and pain. The mechanism may be to inhibit the activation of NF-κB and SP/NK1 receptor signaling pathways by inhibiting TRPV1.

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Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia—Nuclear Factor κB Signaling Pathway

Cited by 5 publications

References 21 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

Effects and mechanisms of acupuncture analgesia mediated by afferent nerves in acupoint microenvironments

Effects of Electroacupuncture on Gastrointestinal Motility Function, Pain, and Inflammation via Transient Receptor Potential Vanilloid 1 in a Rat Model after Colonic Anastomoses

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