Effect of High-definition Transcranial Direct Current Stimulation on Conditioned Pain Modulation in Healthy Adults: A Crossover Randomized Controlled Trial

The disorder of the conditioned pain modulation (CPM) system is one of the main causes of pain perception in individuals. High-definition transcranial direct current stimulation (HD-tDCS) targeting specific brain areas was indicated to have an analgesic effect possibly by activating the endogenous pain inhibition pathway evident in CPM. However, discrepancies were found in previous limited studies of varied homogeneity and quality. Therefore, the present study applied 2 mA HD-tDCS (20 min) in the left primary motor cortex (M1) among 35 healthy adults with a blinded crossover study design, to investigate its effectiveness on optimizing the analgesic effect in healthy individuals through assessing changes of the CPM. The univariate and multivariate general linear models were used to evaluate the intervention effect between-group on the Δ-value (after-intervention minus before-intervention) during CPM (primary outcome), pressure pain threshold (PPT), and cold pressure threshold (CPT) (secondary outcome), respectively. A significant between-group difference in Δ-CPM was found for active stimulation. HD-tDCS significantly improved the analgesic efficiency of Δ-CPM, compared with the sham control, after adjusting the confounding factors including age, gender, psychological status, as well as the sequence effect. The changes of CPM were positively correlated with the total physical activity volume. In conclusion, our findings provide evidence support to the effectiveness of HD-tDCS on endogenous pain modulation among healthy adults. Further studies are required to explore the analgesic effect of tDCS among patients with chronic pain, thereby facilitating optimal chronic pain management.