Chronic low back pain (CLBP) involves pain-related changes in sensory processing, motor control, and broader neurobiological function. The primary somatosensory cortex (S1) is a relevant neuromodulation target because it contributes to sensory-discriminative pain processing and exhibits maladaptive plasticity in chronic pain states. However, S1-targeted high-definition transcranial direct current stimulation (HD-tDCS) has been insufficiently studied in CLBP. To determine whether S1-targeted HD-tDCS combined with core stability training reduces pain intensity and pain-related disability in adults with CLBP, and to explore associated changes in paraspinal muscle biomechanical properties, resting-state EEG activity, and serum metabolites. In this randomized, double-blind, sham-controlled trial, 36 adults with CLBP received active or sham S1 HD-tDCS combined with a standardized 4-week core stability training program. Pain-related scale was assessed using the VAS, ODI, RMDQ and FABQ. Secondary outcomes included biomechanical properties of the lumbar erector spinae and multifidus measured using MyotonPRO. Exploratory outcomes included resting-state electroencephalographic alpha-band power spectral density (PSD) and phase-locking value (PLV) connectivity, as well as untargeted serum metabolomics in a subset of participants. Compared with sham stimulation, active S1 HD-tDCS was associated with greater reductions in VAS, ODI, RMDQ and FABQ scores after treatment. The active group also showed larger decreases in lumbar erector spinae and multifidus tone and stiffness, along with greater improvement in elasticity. Resting-state EEG demonstrated increased alpha-band PSD across frontal, central, and parieto-occipital regions and reduced alpha-band PLV connectivity after active stimulation. In the metabolomics subset, active treatment was associated with greater reductions in circulating L-glutamate and enrichment of ferroptosis-related pathways. Changes in pain intensity were correlated with changes in paraspinal muscle stiffness, central alpha-band PSD, and L-glutamate levels. S1-targeted HD-tDCS combined with core stability training may improve short-term pain intensity and pain-related disability in adults with CLBP. The accompanying muscular, electrophysiological, and metabolomic findings were consistent with the clinical changes. These findings support S1-targeted HD-tDCS as a potential adjunct to exercise-based rehabilitation in CLBP. Chinese Clinical Trial Registry, ChiCTR2300076620 (Registration date 2023-10-13).
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