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D'Andrea G, Terrazzino S, Leon A, Fortin D, Perini F, Granella F, Bussone G. Elevated levels of circulating trace amines in primary headaches. Neurology. 2004;62: 1701-1705.

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.

Comment: Dr. D'Andrea's conclusion are consistent with the fact that the putative generator for cluster, discovered by May, Goadsby et al is in the hypothalamus.—Stewart J. Tepper

This is an important clinico-pathological paper from Professor Bussone's group. For me it raises important questions. Do these vasoactive amines provide the basis for separating out a more “vascular” type of headache, such as Cluster with its nasal congestion, conjunctival injection, and lacrimation? Might these amines be transported via platelets to act as surrogate false transmitters when taken up by sympathetic nerves? These complimentary studies are important alongside the imaging work in order to complete the jigsaw puzzle.—David S. Millson
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Document Type: Research Article

Publication date: November 1, 2004

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