Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine

This paper is designed to provide concepts and stimulate directions for further investigation of menstrual migraine. On the basis of experimental studies and literature review, we propose that abnormalities in how estrogen modulates neuronal function in migraine are due to a mismatch between its gene-regulation and membrane effects. In the interictal phase when estrogen levels peak, increased neuronal excitability is balanced by homeostatic gene regulation in brain cortex, and nociceptive systems. When levels fall at menses, mismatch in homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated hyperexcitability of cell membranes, sensitizing neurons to triggers that activate migraine attacks. At the trough of estrogen levels, the down-regulating effect on inflammatory genes is lost and peptide modulated central sensitization is increased as is pain and disability of the migraine attack.