• There has long been a controversy over the cause of trigeminal neuralgia. Most clinical data favor a peripheral cause. However, most of the experimental data tend to favor a central mechanism. Drugs that are effective in the treatment of trigeminal neuralgia facilitate segmental inhibition in the trigeminal nucleus, as well as depressing excitatory transmission. The most plausible hypothesis to reconcile all of these observations is that trigeminal neuralgia has a peripheral cause and a central pathogenesis. Chronic irritation of the trigeminal nerve apparently leads to both a failure of segmental inhibition in the trigeminal nucleus, and ectopic action potentials in the trigeminal nerve. This combination of increased firing and impaired efficiency of inhibitory mechanisms leads to paroxysmal discharges in the trigeminal nucleus, which are perceived as attacks of trigeminal neuralgia when they involve nociceptive trigeminothalamic-relay neurons.