Introduction The involvement of the serotonergic system of the brainstem raphe in the pathogenesis of migraine is discussed. Here we studied brainstem alterations in migraineurs using transcranial sonography and examined their relation to clinical features and self-medication. Methods We investigated 51 migraineurs (11 men, 40 women, mean age 29.7 ± 11.9 years) and 32 healthy individuals without history of headache or depressive disorder (eight men, 24 women, mean age 34.4 ± 13.0 years). Transcranial sonography was performed in an investigator-blinded fashion. Midbrain raphe echogenicity was quantified using digitized analysis. Migraine characteristics and the use of analgesics were evaluated by applying validated questionnaires. Eight migraineurs underwent neurophysiologic evaluation of contingent stimulus-related cortical potentials. Results Echo-reduced midbrain raphe was detected in 27 (53%) migraineurs, but only six (19%) control subjects (odds ratio = 4.87, p = 0.002). Lower raphe echogenicity correlated with both higher amplitude of terminal contingent negative variation (Spearman test, r = 0.76, p = 0.028) and higher use of analgesic drugs ( r = -0.45, p = 0.011), but not with use of triptans or with migraine frequency or severity (all p > 0.2). Compared to migraineurs without aura, migraineurs with aura had enlarged third ventricles (t-test, p = 0.014), while the lateral ventricle widths did not differ ( p = 0.62). Conclusions Midbrain raphe alteration is frequent in migraineurs and relates to self-medication behavior. This alteration may reflect the dysfunction of serotonergic raphe nuclei.
Keywords: Migraine; analgesics; brainstem raphe; serotonin; transcranial ultrasound; triptans.