title: The role of tyrosine metabolism in the pathogenesis of chronic migraine.
abstract: OBJECTIVE
  The pathogenesis of chronic migraine (CM) remains largely unknown. We hypothesized that anomalies of tyrosine metabolism, found in migraine without aura (MwwA) patients, play an important role in the transformation of MwwA into CM, since the increase in the number of MwwA attacks is the most predisposing factor for the occurrence of CM.
  
  
  METHODS
  To test our hypothesis we measured the plasma levels of dopamine (DA), noradrenaline (NE) and trace amines, including tyramine (TYR) and octopamine (OCT), in a group of 73 patients with CM, 13 patients with chronic tension-type headache (CTTH) and 37 controls followed in the Headache Centers of the Neurology Departments of Asti, Milan and Vicenza hospitals in Italy.
  
  
  RESULTS
  The plasma levels of DA and NE were several-fold higher in CM patients compared with control subjects ( P  > 0.001). The plasma levels of TYR were also extremely elevated ( P  > 0.001); furthermore, these levels progressively increased with the duration of the CM.
  
  
  CONCLUSIONS
  Our data support the hypothesis that altered tyrosine metabolism plays an important role in the pathogenesis of CM. The high plasma levels of TYR, a potent agonist of the trace amine associated receptors type 1 (TAAR1), may ultimately down-regulate this receptor because of loss of inhibitory presynaptic regulation, therein resulting in uncontrolled neurotransmitter release. This may produce functional metabolic consequences in the synaptic clefts of the pain matrix implicated in CM.
authors.affiliation: Research and Innovation (R&I) s.r.l., Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Amico
authors.forename: Gennaro
authors.initials: G
authors.lastname: Bussone
authors.forename: Andrea
authors.initials: A
authors.lastname: Bolner
authors.forename: Marco
authors.initials: M
authors.lastname: Aguggia
authors.forename: Maria G
authors.initials: MG
authors.lastname: Saracco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Galloni
authors.forename: Valentina
authors.initials: V
authors.lastname: De Riva
authors.forename: Davide
authors.initials: D
authors.lastname: Colavito
authors.forename: Alberta
authors.initials: A
authors.lastname: Leon
authors.forename: Valeria
authors.initials: V
authors.lastname: Rosteghin
authors.forename: Francesco
authors.initials: F
authors.lastname: Perini
mesh_terms: D000328:Adult; D002908:Chronic Disease; D004298:Dopamine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D009655:Octopamine / Q000097:blood; D014439:Tyramine / Q000097:blood; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D009655:Octopamine; D014443:Tyrosine; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine
keywords: Chronic migraine; dopamine; noradrenaline; octopamine; tyramine