Abstract: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique known for its reversibility, high safety, and patient compliance. It holds promise as a potential non-pharmacological method for analgesia. Previous studies have primarily focused on applying tDCS to the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1) for pain modulation. However, the analgesic effect of tDCS has shown unsatisfactory results with significant variation among individuals, possibly due to the complexity of the pain neural network and the limited targeting of previous tDCS interventions. To improve the efficacy of tDCS in pain relief, the present study used dual-target tDCS technology to simultaneously modulate the DLPFC and M1, with the aim of investigating the analgesic effects and advantages of this approach.
In Experiment 1, a total of 80 healthy participants were double-blind, randomly allocated to receive either lDLPFC+rM1-tDCS, lDLPFC-tDCS, rM1-tDCS, or Sham-tDCS. The perception of transient pain induced by thermal stimulation and pressure pain thresholds were assessed before and after tDCS application. Dual-target tDCS demonstrated a significant analgesic effect on low-intensity transient pain and pressure pain thresholds, surpassing the effects observed in the lDLPFC-tDCS or rM1-tDCS groups. Furthermore, we found a significant correlation between the analgesic effects of dual-target tDCS on transient pain and participants' pain fear trait. Specifically, the higher the scores on the participants' fear of pain questionnaire, the greater the analgesic effects.
In Experiment 2, a total of 26 participants double-blinded underwent three distinct intervention conditions: lDLPFC+rM1-tDCS (Dual-target), lDLPFC or rM1-tDCS (Single-target), and Sham. The sequence of these conditions was randomized, with a minimum interval of seven days between sessions. The perception of sustained pain induced by capsaicin was assessed during tDCS modulation and 30 minutes post-stimulation. During and after the tDCS modulation, the pain intensity scores in the dual-target tDCS group were significantly lower than those in the sham stimulation group and the single-target tDCS group.
Data from Experiments 1 and 2 demonstrated that dual-target tDCS exhibited a significant analgesic effect on transient pain, sustained pain, and pressure pain thresholds. This analgesic effect was superior to that observed in the single-target tDCS group, supporting the theory of multi-pathway parallel processing in the pain neural network and providing evidence for the potential application of dual-target tDCS in pain treatment.

Key words: transcranial direct current stimulation, dual-target tDCS, analgesic, dorsolateral prefrontal cortex, primary motor cortex.