Prefrontal transcranial direct current stimulation enhances the analgesic effects of attention bias modification: a randomized controlled trial

This study aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) augmented the effect of attentional bias modification (ABM) on pain perception and to explore the potential neuroimaging mechanism by functional infrared spectroscopy (fNIRS). This randomized, single-blind, and parallel-controlled trial enrolled 46 healthy volunteers who were then randomly assigned to two groups, namely active HD-tDCS combined with ABM and sham HD-tDCS combined with ABM groups. The pressure pain threshold (PPT), cold pain threshold, cold pain tolerance, pain intensity, pain unpleasantness, and attentional bias were measured before and after the intervention. fNIRS was used to monitor cerebral hemodynamic responses during repeated cold pain stimulation tasks. Compared to the sham group, the active HD-tDCS plus ABM group demonstrated significantly greater improvements in PPT. Mixed-design ANOVA revealed significant Time × Group interactions for PPT at both the forearm and leg sites. Simple effects analyses showed that PPT significantly increased from pre- to post-intervention in the active group (forearm: p < 0.001; leg: p < 0.001), whereas no significant change was observed in the sham group for the forearm (p = 0.597) and only a small increase was observed at the leg site (p = 0.036). Between-group differences at post-intervention were not significant. Cold pain unpleasantness ratings also demonstrated a significant Time × Group interaction (p = 0.011), with decreases in the active group (p < 0.001) but not in the sham group (p = 0.305); at post-intervention, the active group reported lower unpleasantness than the sham group (p = 0.025). No significant group or interaction effects were observed for cold pain threshold, cold pain tolerance, pain intensity, or attentional bias. Our findings showed that active HD-tDCS combined with ABM training enhanced the analgesic effect of ABM training and reduced pain unpleasantness rating. The analgesic effect may be associated with changes in the activation of prefrontal cortex. However, this effect may not be mediated by modifying the direction of pain attention bias. Further experiments are needed to clarify the analgesic effect of HD-tDCS combined with ABM training on those with clinical pain.