Long-Lasting Changes of Repeated Anodal Transcranial Direct Current Stimulation in Decreasing Chronic Pain in Patients with Multiple Sclerosis: A Case Series

Background: Pain affects 50–75% of individuals with multiple sclerosis (MS) and is more common than in the general population. Chronic pain is difficult to manage and may involve motor cortical and sensorimotor network alterations. Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been explored as a neuromodulatory approach, although its effects and mechanisms remain unclear. Objective: This case series describes longitudinal changes in pain and anxiety following repeated anodal tDCS over left M1 in six individuals with MS-related chronic pain and descriptively reports concurrent changes in transcranial magnetic stimulation (TMS)-derived neurophysiological measures. Methods: Six adults with MS and chronic pain (≥4/10) received 1 mA anodal tDCS over M1 (10 min stimulation, 25 min interval, 10 min stimulation) in two 5-day blocks separated by 2 weeks (10 sessions total), with usual care maintained. Pain and anxiety (0–10) were assessed before and after sessions and at follow-up. TMS assessed corticospinal excitability and intracortical inhibition and facilitation at baseline, post blocks, and at follow-up. Results: Marked inter-individual variability was observed in clinical and neurophysiological trajectories following repeated anodal tDCS. Response patterns included immediate improvement after stimulation blocks, delayed improvement after the second block, and transient rebound during the inter-block interval. TMS-derived measures showed heterogeneous changes, with no consistent correspondence with clinical outcomes. Conclusions: This case series describes variable changes in pain, anxiety, and neurophysiological measures following repeated anodal tDCS over M1 in MS-related chronic pain. The findings are observational and highlight inter-individual variability, supporting further controlled studies.