Cerebral blood flow-based evidence for mechanisms of low- versus high-frequency transcutaneous electric acupoint stimulation analgesia: A perfusion fMRI study in humans

• Forty-six subjects were treated with 2-, 100-Hz TEAS or MTEAS.
• A combined ASL-fMRI scanning and pain threshold testing model was performed.
• TEAS-analgesia started at 20 min during the treatment, and MTEAS was not effective.
• CBF and regional CBF revealed a trend of early activation with later inhibition.
• Key regions related to 2- and 100-Hz TEAS-analgesia are distinct and overlapping.

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 4.5 min before treatment, at 10, 20, and 30 min during treatment and 4.5 min 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 4.5 min. The analgesic effect was observed in both the TEAS groups; the analgesic affect was not found in the MTEAS group. The effect started at 20 min 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.