Enhanced Pain Expectation in Migraine: EEG-Based Evidence for Impaired Prefrontal Function

Background Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. Objective This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. Methods In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. Results A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9V) and unchanged ones in MOAs (1.1V) but not in controls (decrease of 5V). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5V and 4.4V, respectively) compared with controls (decrease of 0.2V). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P<.05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P<.05) and concern of upcoming migraine attacks (P<.05) in MWAs, and with frequency of migraine attacks in MOAs (P<.05). Conclusions Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks.