Resting-state local brain functional synchronization after a single trigger-zone stimulation: with versus without evoked pain in classical trigeminal neuralgia patients

Classical trigeminal neuralgia (CTN) is characterized by transient, stimulus-evoked pain attacks, but post-stimulation changes in local brain synchronization remain unclear. We characterized static and dynamic local functional synchronization at baseline and during resting-state scans initiated after a single trigger-zone stimulation. Baseline analyses included 44 healthy controls (HC), 80 CTN patients with stimulation-evoked pain (CTN _pain ), and 68 CTN patients without evoked pain (CTN _no_pain ). Longitudinal analyses included 39 HC, 75 CTN _pain patients, and 64 CTN _no_pain patients completed all the three resting-state fMRI sessions: baseline, a scan initiated within 5 seconds after stimulation, and a scan initiated 30 minutes later. The first 20 seconds of each time series were discarded. Regional homogeneity, coherence-based regional homogeneity, and their dynamic measures (ReHo, CoReHo, dReHo, and dCoReHo) were assessed using voxel-wise group/time analyses; exploratory region of interest (ROI)-level mixed-effects models tested group × time interactions. At baseline, group differences were observed in Frontal_Med_Orb_R, Insula_L/R, and Hippocampus_R/L. Insula_R dReHo and Frontal_Med_Orb_R ReHo differed between CTN _pain and CTN _no_pain patients. Within-group post-stimulation changes were limited in HC and broader in both CTN subgroups. Exploratory ROI-level sensitivity analyses identified seven group × time interactions that remained significant after metric-specific Bonferroni correction. Exploratory imaging-clinical analyses indicated that imaging measures associations with pain scores in CTN _pain patients and quality of life, anxiety and depression scores in CTN _no_pain patients. CTN subgroups defined by the observed pain-evocation outcome differed in baseline and temporal measures of resting-state local synchronization. Baseline Insula_R dReHo was the subgroup-associated measure but should not be interpreted as causal or predictive. Exploratory group × time interactions and imaging-clinical correlations provide preliminary evidence that requires independent replication. These findings reflect post-stimulation resting-state alterations rather than acute activation.