title: Cerebral blood flow-based evidence for mechanisms of low- versus high-frequency transcutaneous electric acupoint stimulation analgesia: a perfusion fMRI study in humans.
abstract: Brain activities in response to acupuncture have been investigated in multiple studies; however, the neuromechanisms of low- and high-frequency transcutaneous electric acupoint stimulation (TEAS) analgesia are unclear. This work aimed to investigate how brain activity and the analgesic effect changed across 30-min low- versus high-frequency TEAS. Forty-six subjects received a 30-min 2, 100-Hz TEAS or mock TEAS (MTEAS) treatment on both behavior test and functional magnetic resonance imaging (fMRI) scan days. On the behavior test day, the pain thresholds and pain-related negative emotional feeling ratings were tested five times - at 4.5min before treatment, at 10, 20, and 30min during treatment and 4.5min after the treatment. On the fMRI scan day, to match the time-points in the behavioral testing session, the cerebral blood flow (CBF) signals were collected and incorporated with five independent runs before, during and after the treatment, each lasting 4.5min. The analgesic effect was observed in both the TEAS groups; the analgesic affect was not found in the MTEAS group. The effect started at 20min during the treatment and was maintained until the after-treatment states. In both TEAS groups, the regional CBF revealed a trend of early activation with later inhibition; also, a positive correlation between analgesia and the regional CBF change was observed in the anterior insula in the early stage, whereas a negative relationship was found in the parahippocampal gyrus in the later stage. The TEAS analgesia was specifically associated with the default mode network and other cortical regions in the 2-Hz TEAS group, ventral striatum and dorsal anterior cingulate cortex in the 100-Hz TEAS group, respectively. These findings suggest that the mechanisms of low- and high-frequency TEAS analgesia are distinct and partially overlapped, and they verify the treatment time as a notable factor for acupuncture studies.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Neuroscience, The Ministry of Education and Ministry of Public Health, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Peking University First Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Acu-moxibustion, China Academy of Chinese Medical Sciences, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Neuroscience, The Ministry of Education and Ministry of Public Health, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Radiology, Peking University First Hospital, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Neuroscience, The Ministry of Education and Ministry of Public Health, Beijing, China. Electronic address: clcui@bjmu.edu.cn.
authors.forename: C
authors.initials: C
authors.lastname: Cui
mesh_terms: D015670:Acupuncture Therapy / Q000379:methods*; D000328:Adult; D000698:Analgesia / Q000379:methods*; D001921:Brain / Q000098:blood supply / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004644:Emotions; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017288:Pain Threshold; D020534:Parahippocampal Gyrus / Q000098:blood supply / Q000502:physiology; D013997:Time Factors; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D066328:Ventral Striatum / Q000098:blood supply / Q000502:physiology; D055815:Young Adult
keywords: acupuncture analgesia; cerebral blood flow; frequency; transcutaneous electric acupoint stimulation