The exact pathogenesis of childhood migraine is not known, but is felt to represent the interaction of several factors: genetic predisposition, environmental predisposition (eg, hormonal and psychosocial influences), physiological and biochemical abnormalities, precipitating factors, and processing of pain impulses.
The trigeminovascular system, referring to the trigeminal innervation of the cranial vessels, has been linked to the pathophysiology of migraine. Activation of trigeminal nerve terminals by various triggers provokes several events, which include (1) the release into the cranial circulation of neuropeptides including calcitonin gene-related peptide (CGRP, a vasodilator peptide), (2) vessel leakage, and (3) mast-cell degranulation. Neuropeptides are thought to play a role in several aspects of migraine, including migraine pain, lowering of the pain-response threshold, and sensitivity to stimuli that are usually not considered uncomfortable--allodynia (eg, discomfort when combing hair). In humans, sumatriptan normalizes elevated levels of CGRP and relieves the headache. Moreover, treatment with an antagonist of CGRP relieves migraine (Edvinsson and Linde 2010). Abnormalities of ion channels leading to neuronal hyperexcitability have been confirmed in familial hemiplegic migraine (Vanmolkot et al 2006). The cortical spreading depression that is a characteristic of migraine with aura has been found to occur in migraine without aura (Sanchez-Del-Rio 2006). Goadsby postulates that migraine is a type of sensory dysmodulation (Goadsby 2007).