Clinical features of central sensitization moderate the effect of repetitive transcranial magnetic stimulation in chronic low back pain

This secondary analysis of a randomized controlled trial investigated whether baseline clinical characteristics moderate the efficacy of repetitive transcranial magnetic stimulation (rTMS) and motor control exercise (MCE) for chronic low back pain (CLBP). One hundred and forty participants were randomized to active or sham rTMS treatment, combined with or without MCE. Six potential effect modifiers (sex, kinesiophobia, self-efficacy, central sensitization features, lumbar instability, and expectation) were assessed at baseline. Linear mixed models tested interaction effects on pain and disability outcomes at 8 weeks following randomization. A significant interaction was found between rTMS and Central Sensitization Inventory (CSI) scores for disability (p = 0.039): participants with high CSI scores (≥ 40) who received active rTMS had worse disability compared to (i) those with high score who received a sham (mean difference 5.66; 95% CI 0.11-11.21), and (ii) those with low CSI scores who received active rTMS (mean difference -7.28; 95% CI, -12.06 to -2.50). No effect modifiers were identified for MCE. Independent of treatment allocation, positive expectations, lower CSI scores, and higher self-efficacy predicted better disability outcomes. Contrary to the initial hypothesis, active rTMS may hinder recovery in CLBP patients with clinical features of central sensitization. If confirmed, CSI screening could inform personalized brain stimulation strategies to avoid detrimental effects. No evidence supported subgroup-specific benefits of MCE. PERSPECTIVE: This article shows that, when compared to sham stimulation, rTMS may attenuate disability improvement in participants with chronic low back pain who exhibit symptoms of central sensitization. If confirmed, these findings highlight the moderating role of sensitization mechanisms and may guide future personalized neuromodulation approaches.