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Elevated levels of circulating trace amines in primary headaches

From the Headache and Comorbidity Center (Dr. D’Andrea, D. Fortin), Department of Clinical Pathology, Este-Monselice Hospital, and Research and Innovation Company (Drs. Terrazzino and Leon), Padova, Headache Center (F. Perini), Neurology Department, Vicenza Hospital, Institute of Neurology (Dr. Granella), University of Parma, and Headache Center (Dr. Bussone), Neurological Institute "C. Besta," Milan, Italy.

Address correspondence and reprint requests to Dr. G. D’Andrea, Headache and Comorbidity Center, Department of Clinical Pathology, Este-Monselice Hospital, via San Fermo 10, 35042 Este (PD), Italy; e-mail: giovinavi{at}libero.it

Background: Trace amines, including tyramine, octopamine, and synephrine, are closely related to classic biogenic amines. They have been hypothesized to promote migraines and other types of primary headaches, but there is no direct evidence supporting this hypothesis.

Methods: Using a multichannel electrochemical high-performance liquid chromatography system, the authors evaluated whether changes in circulating trace amines occur in subjects with migraine (with or without aura) during headache-free periods as well as in patients with cluster headache (CH) during the remission and active phases as compared with healthy control subjects.

Results: Plasma levels of all trace amines were significantly higher in CH patients, in both the remission and the active phases, when compared with control subjects or subjects with migraine. In addition, intraplatelet levels of octopamine, synephrine, and tyramine were higher in CH patients than in control subjects. In migraine patients, plasma levels of octopamine and synephrine were higher compared with controls, although in migraine with aura, the difference was not significant.

Conclusions: Whereas the elevation of plasma trace amine levels in both migraine and CH supports the hypothesis that disorders of biogenic amine metabolism may be a characteristic biochemical trait in primary headache sufferers, the observation that such alterations are more prominent in patients with CH than migraine patients suggests that they may reflect sympathetic or hypothalamic dysfunction.

Received September 9, 2003. Accepted in final form January 16, 2004.

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