The Neural Mechanisms of rTMS and Placebo Effects in Trigeminal Neuralgia: Evidence From fMRI Network Dynamics.

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been suggested to possess analgesic properties, yet its efficacy in treating trigeminal neuralgia (TN) remains uncertain. Methods: In this randomized, double-blind trial, thirty-four patients were randomly allocated to one of three groups: active M1-targeted rTMS, sham stimulation, or active stimulation of the dorsolateral prefrontal cortex (dlPFC) as a control. The treatment protocol spanned two weeks, consisting of two 5-day stimulation sessions separated by a 2-day interval. MRI and clinical outcomes (VAS, Hamilton Anxiety/Depression Scales) were assessed pre-/post-intervention and at one-month follow-up. Results: Significant reductions in pain, anxiety, and depression occurred across all groups. Neuroimaging revealed decreased insular cortex activation universally, while increased frontal lobe activity emerged specifically in sham and control groups. Notably, no intergroup differences in clinical outcomes were observed despite distinct neural pathways, specifically involving the insula rather than the prefrontal cortex. Conclusion: In the active rTMS group, clinical improvements were associated with modulation of the insula, reflecting targeted neurophysiological effects. In contrast, improvements in the sham group were linked to increased prefrontal and orbitofrontal cortex activation, consistent with placebo-related mechanisms. Significance: This study unveils the critical role of cognitive-emotional pathways in rTMS efficacy, urging integration of neurobiological and psychological strategies for TN therapies.