Anti-inflammatory Effect Of Acupuncture Research Articles

The anti-inflammatory effect of acupuncture on peripheral inflammatory cytokines in patients with major depressive disorder: A systematic review and meta-analysis

There is robust evidence that inflammation is closely associated with major depressive disorder (MDD). The antidepressant effect of acupuncture has been associated with favorable changes in peripheral levels of inflammatory cytokines. However, the findings of these studies were not consistent. This systematic review and meta-analysis were performed to explore the peripheral inflammatory cytokines of acupuncture in treating MDD. The study protocol was registered at PROSPERO, CRD42021289207. We conducted a systematic search for eligible randomized controlled trials (RCTs) that reported acupuncture as an intervention for patients with MDD. The outcome of interest was changes in inflammatory cytokine levels measured before and after the intervention. We searched electronic databases including PubMed, Embase, Cochrane, SinoMed, Wanfang, China National Knowledge Infrastructure (CNKI), and Chongqing VIP (CQVIP). Nine studies including 848 patients were eligible and included. The findings from two studies suggest that acupuncture may lead to changes in inflammatory cytokine levels, irrespective of comparisons with sham acupuncture or Selective Serotonin Reuptake Inhibitors (SSRIs) and Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). While the small sample size, no firm conclusions can be drawn yet. Compared with SSRIs/SNRIs alone, the pooled effect estimation indicates acupuncture combined with SSRIs/SNRIs decreased levels of pro-inflammatory cytokines IL-6, TNF-α and IFN-γ, and elevated levels of anti-inflammatory cytokines IL-4 and IL-10. This study demonstrates that acupuncture appears to have an efficacy in producing anti-inflammatory effects in individuals with MDD.

Acupuncture at ST36 ameliorates experimental autoimmune encephalomyelitis via affecting the function of B cells

Acupuncture at ST36 can alleviate a variety of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), while the specific mechanism for the treatment of EAE is not clear. In this study, we found that acupuncture at ST36 can significantly increase the excitability of splenic sympathetic nerve, and promote the differentiation of peripheral B and CD4+T cells in the anti-inflammatory direction. After blocking the splenic sympathetic nerve with 6-OHDA, this anti-inflammatory effect of acupuncture is partially reversed. In addition, the results of western blot and qPCR showed that acupuncture at ST36 simultaneously activated the β2-AR-cAMP signaling pathway in the splenic B and CD4+T cells, and this activation was more significant in B cells. In vitro, when CD4+T cells were cultured alone, norepinephrine (NE) had no significant effect on their differentiation. While in the presence of B cells, NE significantly promotes the anti-inflammatory differentiation of B and CD4+T cells. Therefore, the above results reveal that acupuncture can relieve EAE by stimulating the sympathetic nerves of spleen, mainly through acting on B cells to mediate anti-inflammatory effects, and indirectly affecting the function of CD4+T cells.

Acupuncture for Primary Dysmenorrhea: A Potential Mechanism from an Anti-Inflammatory Perspective.

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women's overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

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

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 stimulation attenuates TNF-α production via vagal modulation in the concanavalin A model of hepatitis.

A growing body of evidence shows that neuronal activity is involved in modulating the efficacy of acupuncture therapy. However, it has been seldom investigated whether neuronal activity following acupuncture stimulation is effective at regulating hepatic inflammation. Using the concanavalin A (ConA) model of hepatitis, we investigated the regulation of inflammatory cytokine tumor necrosis factor (TNF)-α in the liver tissue and the blood after acupuncture stimulation at ST36. Mice were subjected to ConA injection, acupuncture stimulation at ST36 by manual acupuncture (MA) or electroacupuncture (EA) procedures, and vagotomy (VNX). Liver tissue and blood were collected for TNF-α analysis. TNF-α mRNA was analyzed by real-time polymerase chain reaction (PCR), and TNF-α, CD11b, CD68, and Erk1/2 proteins were analyzed by Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. TNF-α mRNA and protein were induced in CD11b-positive hepatic cells and the plasma at 6-24 h after ConA injection. The application of MA or EA was very effective at attenuating the production of TNF-α. Anti-inflammatory effects of acupuncture were greatly suppressed by VNX in ConA-injected animals, suggesting the requirement of vagus nerve activity in acupuncture-mediated anti-inflammatory responses. Electrical stimulation of the sciatic nerve (SNS) resulted in an anti-inflammatory effect similar to acupuncture stimulation. In parallel with TNF-α, production of phospho-Erk1/2, which was induced in the liver tissue, was downregulated by MA and EA in liver cells. The regulatory effects of acupuncture stimulation on inflammatory responses in the liver may be modulated through the activation of the vagus nerve pathway.

Correlation between ischemic myocardial injury and inflammatory reaction, and anti-inflammatory effect of acupuncture

The inflammatory reaction induced by ischemic myocardial injury (IMI) is divided into three phases, i．e. the inflammatory phase, the fibrous proliferative phase and the stable phase. The appropriate inflammatory reaction effectively removes the fragments of myocardial cells, which is the essential phase in the pathological progression of myocardial ischemia (MI). However, the excessive inflammatory reaction may aggravate the myocardial injury. For this reason, the immediate control of the post-injury inflammatory reaction is the principal therapeutic measure and the research hotspot at the present. Acupuncture intervention has been demonstrated to have positive roles in relieving MI and inflammatory reaction by suppressing myocardial inflammatory cytokines (suppressing IL-1β， TNF-α， IL-8, etc.), adjusting inflammatory reaction pathway (NF-κB signaling, TGF-β， etc.)and activating cholinergic anti-inflammatory pathway. Therefore, it is feasible to explore the underlying mechanism of acupuncture therapy in protecting ischemic myocardium based on anti-inflammatory efficacy.

The anti-inflammatory effect of acupuncture and its significance in analgesia

In the mechanisms of acupuncture analgesia, an important aspect often overlooked is the anti-inflammatory effect of acupuncture, which is mainly attained through the self-limiting inflammatory response-inflammatory reflex and its regulation of hypothalamic-pituitary-adrenal(HPA) axis and autonomic nerve system (the vagus nerve and the sympathetic postganglionic fiber). The significance of anti-inflammatory effect of acupuncture in analgesia is manifested twofold: The first, inflammatory nociceptive pain is a major type of chronic pain. The second, neurogenic inflammation is the mechanism by which certain acupoints or acu-reflex points (ARPs) are formed at the body surface and have short-cut connections to the pathological focus. Selecting ARPs and applying appropriate sensory stimulation or local microtrauma (affected by different needling means or stimulation parameters), combined with low-frequency electrical stimulation or the vagus stimulation in the concha region, are helpful to strengthen the anti-inflammatory and analgesic effect of acupuncture.

Efecto terapéutico de la acupuntura en la amigdalitis

ObjectiveTo determine the analgesic and anti-inflammatory effect of acupuncture in patients with acute and chronic tonsillitis. Patients and MethodA short, longitudinal study was conducted on clinical cases of intervention in a private acupuncture clinic. A treatment protocol was used, with classical Chinese acupuncture points and additional therapy with a 7-point hammer (plum blossom). A total of 52 patients with tonsillitis were attended in the private medical acupuncture clinic. Patients who had received corticosteroid therapy were excluded. ResultsAt the end of the 3-day treatment, the odynophagia and oropharyngeal congestion was totally eliminated in 88.5%, while the symptomatology remained mild in the remaining 11.5% of the patients. Furthermore, 75% of patients showed a complete remission of tonsil hypertrophy, while 25% of them remained with mild tonsillar hypertrophy. ConclusionsThe treatment of tonsillitis with classical Chinese acupuncture was effective for the control of its main signs and / or symptoms, such as odynophagia and tonsil hypertrophy, in most patients. However, there was a lower percentage of patients who did not achieve total healing.

Antagonism of cannabinoid receptor 1 attenuates the anti-inflammatory effects of electroacupuncture in a rodent model of migraine.

The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials. Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor. To investigate whether CB1 receptors mediate the anti-inflammatory effects of EA on migraine attacks. A migraine model was produced in Sprague-Dawley rats by unilateral electrical stimulation of the trigeminal ganglion (TGES). Rats received EA daily on the 5 days preceding TGES with (TGES+EA+SR141716 group) or without (TGES+EA group) intraperitoneal injections of the CB1 receptor antagonist SR141716. Another group of TGES rats (TGES+MA group) and a non-TGES sham-operated group of rats (Sham+MA group) received minimal acupuncture (MA). Calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) concentrations were determined in serum obtained from the ipsilateral jugular vein at initiation of TGES and 5 min after. Postmortem interleukin (IL)-1β and cyclooxygenase (COX)2 protein levels in the trigeminal ganglion (TG) and plasma protein extravasation (PPE) in the dura mater were assessed. TGES induced increases in serum CGRP and PGE2 levels (TGES+MA vs baseline and vs Sham: all p<0.001), as well as IL-1β and COX2 protein expression in the TG, and neurogenic PPE levels (TGES+MA vs Sham+MA: all p<0.001). EA attenuated TGES-induced increases in the levels of these proteins (TGES+EA vs TGES+MA: all p<0.001). CB1 receptor antagonism reversed the effects of EA (TGES+EA+SR141716 vs TGES+EA: all p<0.05). CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.

Acupuncture and Immunity

As a traditional therapy applied for thousands of years, acupuncture has recently been attracting more and more investigators throughout the world. In the theory of traditional Chinese medicine, it is proposed that acupuncture can strengthen the human body to resist diseases by puncturing needles at certain points. The characteristic that acupuncture enhances resistance is closely related with the immune system, which functions in defense, homeostasis, and surveillance. More and more research has revealed that acupuncture can regulate immunity, for example, to enhance anticancer and antistress immune function and exert anti-inflammation effects. This may be the basis of acupuncture in preventing and treating later diseases. This special issue was developed to stimulate the continuing efforts in promoting the research on acupuncture and immunity. The acupuncture point ST36 (Zusanli) is widely applied in immune-related diseases. In “Electroacupuncture at Bilateral Zusanli Points (ST36) Protects Intestinal Mucosal Immune Barrier in Sepsis” M. Zhu et al. reported that EA preconditioning at ST36 obviously ameliorated CLP-induced intestinal injury and high permeability and exerted protective effects on intestinal mucosal immune barrier by increasing the concentration of sIgA and the percentage of CD3+, γ/δ, and CD4+ T cells and the ratio of CD4+/CD8+ T cells, which eventually decreased the mortality of sepsis. “Moxibustion and Acupuncture Ameliorate Crohn's Disease by Regulating the Balance between Th17 and Treg Cells in the Intestinal Mucosa” by C. Zhao et al. provided evidence from a randomized controlled clinical trial that moxibustion and acupuncture regulated the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restored the balance between these immune cell subsets, providing the basis for clinical application of treatment for CD. “Herb-Partitioned Moxibustion Regulates the TLR2/NF-κB Signaling Pathway in a Rat Model of Ulcerative Colitis” by X. Wang et al. assessed the regulation of the TLR2/NF-κB signaling pathway by herb-partitioned moxibustion in the intestinal mucosa of rats with ulcerative colitis (UC). It was reported that herb-partitioned moxibustion modulated the excessive local immune response by inhibiting TLR2 signaling, thereby promoting the repair of damaged colonic mucosa. “Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture” by J. L. McDonald et al. reviewed both demonstrated and proposed anti-inflammatory effects of acupuncture and analyzed the complex crosstalk between receptors during inflammation to elucidate the mediators and signaling pathways activated by acupuncture. Researches with new advances which demonstrated that acupuncture activated a novel cholinergic anti-inflammatory pathway and chemokine-mediated proliferation of opioid-containing macrophages in inflamed tissues were also included. “Immunoregulation on Mice of Low Immunity and Effects on Five Kinds of Human Cancer Cells of Panax japonicus Polysaccharide” by Z. Jie et al. investigated the immunoregulative effects of Panax japonicus polysaccharide (PJPS) on mice of low immunity. The results indicated that PJPS significantly improved the immune function of mice processed by cyclophosphamide and PJPS did not work on the five kinds of human cancer cells. In summary, this issue provides different evidence presented by diverse authors covering several topics related to advances in acupuncture for inflammation or immune diseases. As inflammation is the coherent pathophysiologic progress in many kinds of diseases, immune system and response of the human body are influenced in diseases such as cancer; the anti-inflammation effect of acupuncture may be a very important underlying mechanism of acupuncture in treating diseases. Moreover, TCM focuses on the theory that prevention before the onset of the diseases or intervening in an early stage of diseases is much better than treating after the onset. Preconditioning by acupuncture which means stimulation with acupuncture before the onset of diseases has been widely applied from ancient time to present clinical practice, proposing a potential field in preventing diseases. Acupoints selection, combination of the acupoints, or different methods of stimulation of acupuncture may result in quite different effects on immune system. Further research is urgently essential to elucidate the relation between acupuncture and immune responses and what kind of stimulation might induce the best effect. Of course, the selected topics and papers are not a comprehensive representation of the area of this special issue. Nonetheless, they represent many-faceted evidence that we have the pleasure of sharing with the readers.

IL-10 cytokine released from M2 macrophages is crucial for analgesic and anti-inflammatory effects of acupuncture in a model of inflammatory muscle pain.

Muscle pain is a common medical problem that is difficult to treat. One nonpharmacological treatment used is acupuncture, a procedure in which fine needles are inserted into body points with the intent of relieving pain and other symptoms. Here we investigated the effects of manual acupuncture (MA) on modulating macrophage phenotype and interleukin-10 (IL-10) concentrations in animals with muscle inflammation. Carrageenan, injected in the gastrocnemius muscle of mice, induces an inflammatory response characterized by mechanical hyperalgesia and edema. The inflammation is initially a neutrophilic infiltration that converts to a macrophage-dominated inflammation by 48 h. MA of the Sanyinjiao or Spleen 6 (SP6) acupoint reduces nociceptive behaviors, heat, and mechanical hyperalgesia and enhanced escape/avoidance and the accompanying edema. SP6 MA increased muscle IL-10 levels and was ineffective in reducing pain behaviors and edema in IL-10 knockout (IL-10(-/-)) mice. Repeated daily treatments with SP6 MA induced a phenotypic switch of muscle macrophages with reduced M1 macrophages (pro-inflammatory cells) and an increase of M2 macrophages (anti-inflammatory cells and important IL-10 source). These findings provide new evidence that MA produces a phenotypic switch in macrophages and increases IL-10 concentrations in muscle to reduce pain and inflammation.

Anti-Inflammatory Effects of Acupuncture

Anti-Inflammatory Effects of Acupuncture

Prospective tests on biological models of acupuncture.

The biological effects of acupuncture include the regulation of a variety of neurohumoral factors and growth control factors. In science, models or hypotheses with confirmed predictions are considered more convincing than models solely based on retrospective explanations. Literature review showed that two biological models of acupuncture have been prospectively tested with independently confirmed predictions: The neurophysiology model on the long-term effects of acupuncture emphasizes the trophic and anti-inflammatory effects of acupuncture. Its prediction on the peripheral effect of endorphin in acupuncture has been confirmed. The growth control model encompasses the neurophysiology model and suggests that a macroscopic growth control system originates from a network of organizers in embryogenesis. The activity of the growth control system is important in the formation, maintenance and regulation of all the physiological systems. Several phenomena of acupuncture such as the distribution of auricular acupuncture points, the long-term effects of acupuncture and the effect of multimodal non-specific stimulation at acupuncture points are consistent with the growth control model. The following predictions of the growth control model have been independently confirmed by research results in both acupuncture and conventional biomedical sciences: (i) Acupuncture has extensive growth control effects. (ii) Singular point and separatrix exist in morphogenesis. (iii) Organizers have high electric conductance, high current density and high density of gap junctions. (iv) A high density of gap junctions is distributed as separatrices or boundaries at body surface after early embryogenesis. (v) Many acupuncture points are located at transition points or boundaries between different body domains or muscles, coinciding with the connective tissue planes. (vi) Some morphogens and organizers continue to function after embryogenesis. Current acupuncture research suggests a convergence of the neurophysiology model, the connective tissue model and the growth control model. The growth control model of acupuncture set the first example of a biological model in integrative medicine with significant prediction power.

Protein array analysis of cytokine levels on the action of acupuncture in carrageenan-induced inflammation

Background: The aim of this study was to investigate the anti-inflammatory effect of acupuncture on acute paw edema induced by carrageenan (CR) injection and to detect differential cytokine responses in response to acupuncture stimulation using protein array technology.Methods: Control group was injected with CR (1%, 50 μl) into the plantar surface of the male Sprague–Dawley rats. Acupuncture group was stimulated with acupuncture at Zusanli (ST36) 30 minutes after CR injection. Rat cytokine antibody array coated with 19 specific cytokine antibodies were probed with protein samples and the relative cytokine levels were investigated.Results: Acupuncture stimulation significantly inhibited the inflammatory response to CR injection. Compared to control group, three cytokines, interleukin-6 (IL-6), β-nerve growth factor (β-NGF) and tissue inhibitors of metalloproteinase-1 (TIMP-1), showed significantly decreased expression levels in the acupuncture group. The other 16 cytokines did not exhibit significant changes between two groups.Conclusion: These results indicate that acupuncture markedly inhibited CR-induced edema and modulated the expressions of certain cytokines in response to CR-induced inflammation. These findings might give us a clue in elucidating the underlying mechanism of anti-inflammatory effect of acupuncture.

Possible Role of Acupuncture in the Treatment of Post-Zoster Limb Pain and Paresis

AbstractBackground: Associations of inflammation with occurrence of pain and paralysis in shingles have been well documented. Thus, the anti-inflammatory effect of acupuncture might improve or hasten pain relief and motor recovery in patients with shingles-associated pain and paralysis.Objective: To describe the possible role of acupuncture in motor deficit recovery and pain relief in a male patient with post-zoster neuralgia and limb paralysis.Case Summary: The patient developed burning pain over his right shoulder followed by red painful vesicles over the right arm and right shoulder weakness. Despite hydrocodone, rofecoxib and gabapentin, these symptoms persisted. His physical examination and laboratory tests were normal except for the deltoid muscle strength of 1/5, and the C4 dermatome rashes. He received a 10-day course of intravenous acyclovir and prednisone, massage therapy, physical and occupational therapy. The rashes resolved. The pain-10/10 in severity-and paralysis persisted, even one month p...

Possible Role of Acupuncture in the Treatment of Post-Zoster Limb Pain and Paresis

Background: Associations of inflammation with occurrence of pain and paralysis in shingles have been well documented. Thus, the anti-inflammatory effect of acupuncture might improve or hasten pain relief and motor recovery in patients with shingles-associated pain and paralysis.Objective: To describe the possible role of acupuncture in motor deficit recovery and pain relief in a male patient with post-zoster neuralgia and limb paralysis.Case Summary: The patient developed burning pain over his right shoulder followed by red painful vesicles over the right arm and right shoulder weakness. Despite hydrocodone, rofecoxib and gabapentin, these symptoms persisted. His physical examination and laboratory tests were normal except for the deltoid muscle strength of 1/5, and the C4 dermatome rashes. He received a 10-day course of intravenous acyclovir and prednisone, massage therapy, physical and occupational therapy. The rashes resolved. The pain-10/10 in severity-and paralysis persisted, even one month post-hospital discharge. In line with the Traditional Chinese Medicine method, 3–4 acupuncture treatments per week were administered to the patient for 3 months. By the end of the 1st month of treatment, the patient muscle strength was 4/5 and his pain was 3/10. By the 3rd month, his muscle strength was 5/5 and his pain was down to 1/10. At the 18-month follow-up, he had normal muscle strength and was off all analgesic drugs.Conclusion: The usefulness of acupuncture in the treatment of shingle-related neuropathic pain and motor paralysis merits further study in a large, controlled clinical trial.