Neural substrate of depression during migraine.

Migraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn and thalamus. We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as stress activate multiple hypothalamic, limbic and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression and the quest for solitude. The network of bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive mechanism of perpetual feedback that drives a migraine attack for many hours and even days.