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      Prolonged Repeated Acupuncture Stimulation Induces Habituation Effects in Pain-Related Brain Areas: An fMRI Study

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          Abstract

          Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.

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          Most cited references48

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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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            Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects.

            Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.
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              Acupuncture analgesia: areas of consensus and controversy.

              Sheng Han (2011)
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                12 May 2014
                : 9
                : 5
                : e97502
                Affiliations
                [1 ]Laboratory of Digital Medical Imaging, Medical Imaging Center, First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, Anhui, China
                [2 ]Department of Acupuncture and Moxibustion, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
                [3 ]Department of Biomedical Engineering, Kyung Hee University, Yongin, Republic of Korea
                [4 ]College of Medical Information engineering, Anhui University of Chinese Medicine, Hefei, Anhui, China
                [5 ]School of Information Science and Technology, University of Science and Technology of China, Hefei, Anhui, China
                [6 ]CAS Key Laboratory of Brain Function & Disease and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China
                Institute of Automation, Chinese Academy of Sciences, China
                Author notes

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

                Conceived and designed the experiments: CL JY KP BQ XZ. Performed the experiments: JY HW SH WZ CX. Analyzed the data: CL HW WZ JB BQ XZ. Contributed reagents/materials/analysis tools: JY KP SH JB CX. Wrote the paper: CL.

                Article
                PONE-D-14-07298
                10.1371/journal.pone.0097502
                4018444
                24821143
                c5d756ce-3353-4f2b-be37-5b75e210d665
                Copyright @ 2014

                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
                : 17 February 2014
                : 16 April 2014
                Page count
                Pages: 10
                Funding
                This study was supported by grants from Anhui Provincial Natural Science Foundation under Grant No. 1208085MH147 ( http://220.178.98.52/zrkxjj/), Major Scientific Projects of Anhui Provincial Education Commission under Grant No. KJ2011ZD05 ( http://www.ahsr.edu.cn/srmis/), the National Natural Science Foundation of China under Grant No. 81202768, 31171083, 31230032 ( http://www.nsfc.gov.cn/Portal0/default152.htm), and the National Key Basic Research and Development Program (973) under Grant No. 2010CB530500 ( http://www.973.gov.cn/Default_3.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Nervous System
                Neuroscience
                Sensory Systems
                Physiology
                Nervous System Physiology
                Physiological Processes
                Medicine and Health Sciences
                Complementary and Alternative Medicine
                Health Care
                Physiotherapy
                Neurology
                Radiology and Imaging

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                Uncategorized

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