Non-Invasive Brain Stimulation for Central Neuropathic Pain: An Exploratory Randomized Sham-Controlled Crossover Trial

Abstract

Background/Objectives: Central neuropathic pain (CNP) is difficult to manage, and comparative evidence for non-invasive brain stimulation is limited. We explored the short-term efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in CNP. Methods: In this randomized, sham-controlled crossover trial, 26 patients were allocated to active or sham stimulation and received high-frequency rTMS (10 Hz, 2000 pulses/session) and anodal tDCS (2 mA, 30 min) over the primary motor cortex for five days each, separated by a 4-week washout. The primary outcome was change in Numerical Rating Scale (NRS) pain intensity at 1 and 4 weeks, analysed using factorial linear mixed-effects models with and without age adjustment. Results: At 1 week, the difference between active and sham rTMS was 0.76 points (95% CI −0.005 to 1.53; p = 0.051) and 0.42 points after age adjustment (95% CI −0.37 to 1.21; p = 0.30). Active tDCS did not differ from sham tDCS, and active rTMS did not differ from active tDCS. No significant differences were found at 4 weeks or in responder analyses. No serious adverse events occurred. Conclusions: In this small exploratory trial, neither rTMS nor tDCS showed statistically significant superiority over modality-matched sham, and no difference between modalities was demonstrated. Adequately powered trials are needed.