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Brain Advance Access originally published online on December 5, 2005
Brain 2006 129(2):543-550; doi:10.1093/brain/awh691
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine

Arnaud Fumal1,2,{dagger}, Steven Laureys1,3,{dagger}, Laura Di Clemente1, Mélanie Boly1,3, Valentin Bohotin1, Michel Vandenheede1, Gianluca Coppola1, Eric Salmon1,3, Ron Kupers4 and Jean Schoenen1,2

Departments of 1 Neurology and 2 Neuroanatomy and 3 Cyclotron Research Center, University of Liège, Liège, Belgium and 4 Aarhus University and University Hospital of Aarhus, Center for Functionally Integrative Neuroscience (CFIN), Aarhus, Denmark

Correspondence to: Arnauld Fumal, University Department of Neurology, CHR Hospital, bvld du XIIeme de Ligne 1, B-4000 Liège, Belgium E-mail: arnaud.fumal{at}ulg.ac.be

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse.

Key Words: PET; orbitofrontal cortex; migraine; addiction; medication overuse headache

Abbreviations: FDG = [18F]fluorodeoxyglucose; FDG-PET = 18F-fluoro-deoxyglucose positron emission tomography; MOH = medication overuse headache; MRI = magnetic resonance imaging; OFC = orbitofrontal cortex; PET = positron emission tomography; rCBF = regional cerebral blood flow; VAS = visual analogue scale

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Received June 6, 2005. Revised August 31, 2005. Accepted October 20, 2005.

{dagger} Both these authors contributed equally to this work.


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