title: Opioid control of the hypothalamus-pituitary-adrenal axis cyclically fails in menstrual migraine.
abstract: To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta-EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta-EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity.
authors.affiliation: University Centre for Adaptive Disorders and Headache (UCADH), University of Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Facchinetti
authors.forename: E
authors.initials: E
authors.lastname: Martignoni
authors.forename: L
authors.initials: L
authors.lastname: Fioroni
authors.forename: G
authors.initials: G
authors.lastname: Sances
authors.forename: A R
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: D000328:Adult; D004723:Endorphins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008597:Menstrual Cycle; D008881:Migraine Disorders / Q000378:metabolism* / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004723:Endorphins; D009270:Naloxone