Maltreatment during childhood increases vulnerability to a host of health disorders, including migraine. Putative mechanisms linking maltreatment and migraine include stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as disruption of other stress-mediating homeostatic systems, including those involving endocannabinoids, monoamine neurotransmitters, oxytocin, and inflammation. Prolonged elevation of glucocorticoids alters the neural architecture of the limbic system, resulting in the structural as well as functional changes described in both maltreatment and in migraine. Although treatment trials for migraine have not stratified participants by abuse history, strategies, such as cognitive behavioral therapy, which alter stress responsivity, may be particularly effective in this subgroup. Some therapies involving the endocannabinoid, serotonergic, oxytonergic, and inflammatory systems are under investigation for migraine. Anti-epileptic drugs such as valproate and topiramate, which are FDA approved for migraine treatment, are also known to interfere with epigenetic changes induced by stress. Discerning the role for this mechanism in treatment of maltreated migraineurs may introduce another therapeutic avenue.
Keywords: Abuse; Adverse childhood experiences; Childhood maltreatment; Cognitive behavioral therapy; Epigenetics; Genetics; Hypothalamic–pituitary–adrenal axis; Inflammation; Migraine; Oxytocin; Serotonin; Stress.