Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network. Author: Niu X1,2, Zhang M2, Liu Z3, Bai L1,4, Sun C1, Wang S1, Wang X1, Chen Z1, Chen H5, Tian J3 Affiliation: <sup>1</sup>1 The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. <sup>2</sup>2 Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. <sup>3</sup>3 Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, China. <sup>4</sup>4 Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. <sup>5</sup>5 Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China. Conference/Journal: Mol Pain. Date published: 2017 Jan Other: Volume ID: 13 , Pages: 1744806916683684 , Special Notes: doi: 10.1177/1744806916683684. , Word Count: 344 Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain. KEYWORDS: Interaction effect; capsaicin pain model; default mode network; electroacupuncture; laterality; placebo analgesia PMID: 28326925 PMCID: PMC5330599 DOI: 10.1177/1744806916683684