Cortical excitability and analgesic effects of multisite transcranial direct current stimulation targeting the motor cortex and cerebellum in fibromyalgia

This double-blind, sham-controlled randomized clinical trial investigated whether a single session of anodal-(a) transcranial direct current stimulation (tDCS), applied over the primary motor cortex (M1), cerebellum (CB), or both, would reduce pain and increase corticospinal excitability more effectively than sham stimulation (s-tDCS). Ninety-two women with fibromyalgia were randomized to a single session of anodal-(a)-tDCS or sham-(s)-tDCS. Primary outcomes were pain intensity, assessed with the Numerical Pain Scale (NPS), and corticospinal excitability, measured by motor evoked potentials (MEP). Compared to sham, a-tDCS significantly reduced NPS scores (Wald χ² = 7.02, df = 1, p < 0.01; d = 0.55, 95% CI 0.08-0.92) and increased MEP amplitude (Wald χ² = 8.37, df = 1, p < 0.01; d = 0.48, 95% CI 0.07-0.89). Post-hoc and interaction analyses indicated that these effects were primarily attributable to M1 stimulation, rather than cerebellar or combined protocols. Anodal tDCS also reduced multidimensional pain interference, as measured by the Brief Pain Inventory (BPI), and reduced the cortical silent period (CSP) in a BDNF-dependent manner. These findings provide mechanistic insights rather than clinical efficacy, showing that a single M1 a-tDCS session-compared to sham, cerebellar, or combined protocols-more effectively reduced pain intensity and interference and modulated cortical excitability in a BDNF-dependent manner.Trial registration: ClinicalTrials.gov. NCT05963321. URL https://clinicaltrials.gov/study/NCT05963321 (Date of registration 27/07/2023).