We conclude a possible pathophysiological process whereby migraine induces an upregulation of Arc expression in the hippocampus and cortex by some means—possibly the effect of inflammatory stimuli on glutamate receptors—which in turn causes a downregulation of presynaptic function and AMPAR-mediated synaptic scaling, leading to an external manifestation of homeostatic synaptic plasticity dysfunction and cognitive dysfunction. This evidence concerns the gene ARC and migraine disorder.