Introduction:
Trigeminal neuralgia (TN) is a severe neuropathic pain disorder characterized by brief, electric shock – like attacks within the trigeminal distribution. Although classically linked to neurovascular compression, recent evidence indicates that its pathophysiology extends beyond peripheral mechanisms to include central sensitization and neuroinflammatory processes.

Aim:
The aim of this review was to analyze the neurophysiological mechanisms of TN, emphasizing the interplay between demyelination, altered ion channel expression, and central plasticity, as well as to present modern diagnostic and therapeutic approaches targeting these mechanisms.

Materials and Methods:
The study is a narrative review drawing on current evidence-based literature concerning the peripheral and central mechanisms of TN, including electrophysiological, neuroimaging, and experimental model data.

Results:
Peripheral demyelination at the root entry zone promotes ectopic discharges and ephaptic transmission between adjacent fibers, while upregulation of voltage-gated sodium channels (Nav1.6, Nav1.7) enhances neuronal hyperexcitability. Central sensitization involves activation of microglia and astrocytes releasing proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, interleukin-6) and neurotrophins (brain-derived neurotrophic factor), contributing to persistent pain. Neuroimaging demonstrates cortical and subcortical reorganization in pain-processing regions. Therapeutic advances include selective sodium and calcium channel blockers and microvascular decompression.

Conclusions:
TN arises from an interplay between peripheral demyelination and central neuroplasticity. Understanding these interconnected mechanisms provides a foundation for more targeted and effective therapeutic strategies that address both neuronal hyperexcitability and neuroinflammation.