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      Effects of acupuncture for the treatment of endometriosis-related pain: A systematic review and meta-analysis

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          Abstract

          Background

          Endometriosis is a multifactorial, oestrogen-dependent, inflammatory, gynaecological condition that can result in long-lasting visceral pelvic pain and infertility. Acupuncture could be an effective treatment for endometriosis and may relieve pain. Our aim in the present study was to determine the effectiveness of acupuncture as a treatment for endometriosis-related pain.

          Methods

          In December 2016, six databases were searched for randomised controlled trials that determined the effectiveness of acupuncture in the treatment of endometriosis-related pain. Ultimately, 10 studies involving 589 patients were included. The main outcomes assessed were variation in pain level, variation in peripheral blood CA-125 level, and clinical effective rate. All analyses were performed using comprehensive meta-analysis statistical software.

          Results

          Of the 10 studies included, only one pilot study used a placebo control and assessed blinding; the rest used various controls (medications and herbs), which were impossible to blind. The sample sizes were small in all studies, ranging from 8 to 36 patients per arm. The mean difference (MD) in pain reduction (pre- minus post-interventional pain level—measured on a 0–10-point scale) between the acupuncture and control groups was 1.36 (95% confidence intervals [CI] = 1.01–1.72, P<0.0001). Acupuncture had a positive effect on peripheral blood CA-125 levels, as compared with the control groups (MD = 5.9, 95% CI = 1.56–10.25, P = 0.008). Similarly, the effect of acupuncture on clinical effective rate was positive, as compared with the control groups (odds ratio = 2.07; 95% CI = 1.24–3.44, P = 0.005).

          Conclusions

          Few randomised, blinded clinical trials have addressed the efficacy of acupuncture in treating endometriosis-related pain. Nonetheless, the current literature suggests that acupuncture reduces pain and serum CA-125 levels, regardless of the control intervention used. To confirm these findings, additional, blinded studies with proper controls and adequate sample sizes are needed.

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          Most cited references37

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          Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

          Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings 1-3 . Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders 3 . Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency 4 , increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders.
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            The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI.

            Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.
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              Immune-inflammation gene signatures in endometriosis patients

              Objective To determine if the molecular profiles of endometriotic lesions contain informative measures of inflammation and immune dysfunction that may contribute to better understanding of the interplay between immune dysfunction and inflammation and their contribution to endometriosis pathogenesis. Design Immune and inflammation transcriptomic analysis with the use of the Nanostring nCounter GX Human Immunology V2 platform (579 human immune and inflammation–related genes and 15 housekeeping genes). Setting Academic university and teaching hospital. Intervention(s) None. Patient(s) Stage III–IV endometriosis patients with infertility (n = 8) and fertile disease-free control women undergoing tubal ligation (n = 8). Menstrual stage was matched to secretory phase in all participants. Main Outcome Measure(s) Immune and inflammation transcriptomics quantification from ectopic endometriotic lesions and matched eutopic endometrium from patients. Endometria of fertile women served as control subjects. Result(s) Our results displayed endometriotic lesions as molecularly distinct entities compared with eutopic endometrium and endometrium of control samples; 396 out of 579 screened immune and inflammation–related genes were significantly different in ectopic tissues compared with control endometrium. Most importantly, eutopic endometrium of the patients displayed a unique molecular profile compared with the control endometrium (91/579 genes were significantly different), particularly of genes involved in regulation of cell apoptosis and decidualization. Conclusion(s) We characterize differential expression of immune-inflammation genes in endometriosis patients, and show molecular distinction of eutopic endometrium of patients compared with control fertile women.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administration
                Role: Formal analysis
                Role: Data curationRole: Formal analysis
                Role: Project administrationRole: SoftwareRole: Supervision
                Role: Project administrationRole: ResourcesRole: SoftwareRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 October 2017
                2017
                : 12
                : 10
                : e0186616
                Affiliations
                [1 ] Department of Gynecology and Obstetrics, Nankai Hospital, Tianjin Academy of Integrative Medicine, Tianjin, China
                [2 ] Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
                [3 ] Department of Neurology, Nankai Hospital, Tianjin Academy of Integrative Medicine, Tianjin, China
                [4 ] Department of Chinese Medicine, Tianjin Hearing Impairment Specialist Hospital, Tianjin, China
                [5 ] Department of Chemical Engineering, University of Florida, Gainesville, Florida, United States of America
                [6 ] Department of Public Health, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
                [7 ] Laboratory of Anatomy, School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
                Stanford University School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8745-7745
                Article
                PONE-D-17-08293
                10.1371/journal.pone.0186616
                5659600
                29077705
                66e5e99a-3621-4127-8d1d-b180f7f43ab1
                © 2017 Xu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 March 2017
                : 4 October 2017
                Page count
                Figures: 7, Tables: 2, Pages: 15
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Complementary and Alternative Medicine
                Acupuncture
                Medicine and Health Sciences
                Pain Management
                Acupuncture
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Database and Informatics Methods
                Database Searching
                Medicine and health sciences
                Complementary and alternative medicine
                Traditional medicine
                Traditional Chinese medicine
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Menstrual Abnormalities
                Dysmenorrhoea
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Pain
                Abdominal Pain
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Pain
                Abdominal Pain
                Medicine and Health Sciences
                Pain Management
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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