Pain mechanisms in trigeminal neuralgia: From peripheral pathology to brain network reorganization and neurosurgical...

Trigeminal neuralgia (TN) involves peripheral neurovascular pathology and may also be associated with maladaptive neuroplastic changes in central nervous system networks. This review synthesizes evidence on peripheral and central pain mechanisms, neuroimaging biomarkers, molecular and transcriptomic correlates, and neurosurgical implications, including emerging neuromodulation strategies.

This narrative review drew on topic-oriented searches of PubMed/MEDLINE, Scopus, and Web of Science conducted between June 27 and July 5, 2026, covering literature published through June 2026. Supplementary targeted searches and reference-list screening were used to identify relevant publications. Evidence was synthesized qualitatively.

Evidence supports a multilevel model of TN involving peripheral pathology and central neuroplastic changes. Neuroimaging studies report structural and functional alterations in sensorimotor, salience, limbic, and default mode networks, alongside disrupted structure-function coupling. Partial restoration of functional connectivity after neurosurgical treatment has been reported, although outcomes vary. Transcriptomic findings link imaging abnormalities to genes involved in ion channel function, synaptic signaling, neuroinflammation, and energy metabolism but remain hypothesis-generating. Transcutaneous electrical nerve stimulation (TENS) may provide short-term analgesic benefit; however, evidence is limited and heterogeneous.

TN may be understood as a disorder involving interactions between peripheral pathology and central nervous system reorganization. Integrating neuroimaging and molecular evidence may inform future patient stratification and neurosurgical decision-making. Individualized neuromodulation remains investigational and requires further clinical validation.