From Neurovascular Compression to Neural Hyperexcitability: Integrating Microanatomy, Electrophysiology, and Computational Neuroscience to Understand Trigeminal Neuralgia and Hemifacial Spasm

Neurovascular compression syndromes (NVCS), including trigeminal neuralgia (TN) and hemifacial spasm (HFS), are characterized by disabling symptoms caused by vascular compression of cranial nerves. Although microvascular decompression is an established treatment, mechanisms linking neurovascular compression to abnormal neural activity remain incompletely understood. In this review, we integrate evidence from microanatomical, electrophysiological, and computational studies to provide a mechanistic framework for NVCS. Chronic vascular compression induces focal demyelination, redistribution of voltage-gated ion channels, ectopic impulse generation, and ephaptic transmission, leading to abnormal neuronal excitation. We further summarize emerging evidence that persistent peripheral hyperactivity may contribute to electrophysiological alterations in central neural circuits. Particular attention is given to computational approaches, including cable theory and axonal interaction models, which offer quantitative insights into abnormal synchronization and cross-excitation among nerve fibers. Recent findings regarding ion channel dysfunction, including familial TN associated with gain-of-function calcium channel variants, are also discussed. Collectively, these findings support an integrated model linking neurovascular compression to clinical manifestations, and highlight the value of combining electrophysiology and computational neuroscience to improve mechanistic understanding and to guide future therapeutic strategies for NVCS.