Neuronal mechanisms during repetitive trigemino-nociceptive stimulation in migraine patients

Habituation deficits in various sensory modalities have been observed in migraine patients in several experimental designs. The underlying neuronal mechanisms are, however, still unknown. Past studies have used electrophysiological measures and focussed on habituation behaviour during one single session. We were interested in how repeated painful stimulation over several days is processed, perceived and modulated in migraineurs. Fifteen migraine patients and 15 healthy controls were stimulated daily with a 20 min trigeminal pain paradigm for eight consecutive days, using functional MRI performed on days one and eight and one follow-up measurement three months later. The results demonstrate that migraine patients did not differ in behavioural pain ratings compared to the controls at any time. However, functional imaging data revealed a significant difference in several brain areas over time. The activity level in the prefrontal cortex (PFC) and the rostral anterior cingulate cortex (rACC) increased in healthy control subjects from day one to day eight, whereas it decreased in migraine patients. These data suggest that several brain areas known to be involved in endogenous pain control show a completely opposite behaviour in migraine patients compared to healthy controls. These brain networks seem not to be disrupted per se in migraine patients but changed activity over time responding to repetitive nociceptive input. The alteration of pain inhibitory circuits may be the underlying mechanism responsible for the dys-functional neuronal filters of sensory input.