Electroacupuncture alleviates inflammatory pain via adenosine suppression and its mediated substance P expression

Zhang, Rong yi; Zhu, Ben fan; Wang, Li kui; Song, Yang; Zhao, Jia gui; Guo, Yan; Zhao, Long; Chen, Shi

doi:10.1590/0004-282x20200078

Cited by 17 publications

(17 citation statements)

References 28 publications

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“… 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. Acupuncture also promotes mast cell degranulation and fibroblast structure remodeling to induce release of ATP, substance P (SP), tryptase, histamine (HA), interleukins, 5-hydroxytryptamine (5-HT), and other substances, which also mediate acupuncture action.…”

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

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“…In CFA-treated rats, EA at ST36 and BL60 reduces the levels of SP, neurokinin-1 receptor (NK-1R), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor (TNF)-α in the DRG by promoting adenosine release and activating the A1Rs of nerve endings at local acupoints. Therefore, it appears that the acupuncture-activated acupoint–A1R pathway contributes to the anti-inflammatory action of acupuncture ( Zhang et al, 2020d ). Further, in CFA-induced rat models of pain, MA at ST36 can directly induce neural regulation by activating the mechanically sensitive transient receptor potential ion channel vanilloid 1 (TRPV1) channel receptors expressed on nerve terminals and immune cells and promote adenosine triphosphate (ATP) release via calcium wave propagation across nearby nerve endings.…”

Section: Microenvironment Regulation At the Acupoint After Acupuncturementioning

confidence: 99%

“…Interestingly, when the dorsal nerve root is cut or an SP receptor antagonist is injected, the inhibitory effect of EA on SP, NK-1R, and other downstream inflammatory factors is attenuated, which significantly reduces the analgesic effect of EA. Hence, EA may also prevent the transmission of pain signals to the CNS by inhibiting the expression of SP in the DRG ( Zhang et al, 2020d ).…”

Section: Acupuncture-induced Inhibition Of Peripheral Sensitivity In Inflammatory Pain Modelsmentioning

confidence: 99%

“…Therefore, it appears that the acupuncture-activated acupoint-A1R pathway contributes to the anti-inflammatory action of acupuncture (Zhang et al, 2020d). Further, in CFA-induced rat models of pain, MA at ST36 can directly induce neural regulation by activating the mechanically sensitive transient receptor potential ion channel vanilloid 1 (TRPV1) channel receptors expressed on nerve terminals and immune cells and promote adenosine triphosphate (ATP) release via calcium wave propagation across nearby nerve endings.…”

Section: Microenvironment Regulation At the Acupoint After Acupuncturementioning

confidence: 99%

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Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain

Dou

et al. 2021

Front. Neurosci.

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Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

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“…15,16 Mounting evidence reveals that the Zusanli acupuncture point is an effective target for EA, which has been involved in regulating chronic neuropathic pain and its implicated inflammatory processes. [17][18][19] Thus, with the goal of developing a new strategy to intervene in CP, the aim of this study was to observe the effect of EA on the inflammatory response and pain management in rats with chronic nonbacterial prostatitis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Electroacupuncture on Alleviating Prostatodynia and Inflammation in Rats with Chronic Nonbacterial Prostatitis

Zhang

Ding

2021

JPR

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Purpose: Chronic prostatitis (CP) is a common urinary disease characterized by a complex sequence of symptoms including prostatodynia, which results in significant physical pain and mental burden to affected patients. Currently, CP has no standard treatment. Thus, physical therapy electroacupuncture (EA) which has been successful in treating several inflammationrelated pain conditions was used to determine its effect on rats with CP. Materials and Methods: Rats were castrated and treated with beta-estradiol for 28 days for CP modeling, and EA was initiated one week after. Following three weeks of treatment, painrelated behavioral testing, mechanical withdrawal threshold, and potential histopathological mechanisms were examined. Results: EA treatment produced a significant antinociceptive effect, effectively increasing the pain threshold of CP rats, and the biochemical results revealed significantly lowered prostatic specific antigen levels. Histopathological results also demonstrated that EA exerted protective properties on prostate morphological changes, as well as decreased inflammation cytokines and oxidative stress molecular expressions in prostate tissue. Furthermore, EA alleviated microglial and astrocyte activation in the dorsal horn of the spinal cord, decreasing CXC motif ligand 1 expressions in activated spinal astrocytes. Conclusion:In conclusion, it was demonstrated that EA alleviated CP-induced pain, which was partly achieved by the downregulation of inflammation, oxidative stress, and spinal cord glial activation.

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Electroacupuncture alleviates inflammatory pain via adenosine suppression and its mediated substance P expression

Cited by 17 publications

References 28 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

Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain

Effects of Electroacupuncture on Alleviating Prostatodynia and Inflammation in Rats with Chronic Nonbacterial Prostatitis

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