A study of adaptive responses in cell signaling in migraine and cluster headache: correlations between headache type and changes in gene expression.

The project was an investigation into whether changes in the expression of G-proteins underlie altered cell signaling in migraine and cluster headache. The basis for this assumption is that altered physiological responses are seen in migraineurs and that differences in cell signaling are detected biochemically in various cell types isolated from peripheral blood. Levels of three G-protein mRNAs--Gs alpha, Gi alpha, and Gq alpha, were quantified in lymphocytes from clinically well-defined migraine and cluster headache patients and correlated with headache type and influence of drug treatment. Gi alpha mRNA was reduced by 50% in all migraine patients compared with control subjects; similarly in patients with or without aura, in patients with a migraine headache at the time of sampling, and patients in a quiescent state. No reduction in the levels of Gs alpha of Gq alpha mRNA were seen in migraine patients. A smaller reduction was seen in cluster headache patients, most marked in those without medication. Levels of Gs alpha mRNA were significantly reduced in cluster headache patients compared with migraine patients. The marked down-regulation of Gi alpha mRNA in migraine, whether quiescent or acute, indicates either an adaptive response to headache in this group of patients or that low levels of Gi alpha mRNA make individuals more susceptible to migraine.