In Medication-Overuse Headache, fMRI Shows Long-Lasting Dysfunction in Midbrain Areas

• Published in: Headache Vol. 52; no. 10; pp. 1520 - 1534
• Main Authors: Ferraro, Stefania, Grazzi, Licia, Muffatti, Riccardo, Nava, Simone, Ghielmetti, Francesco, Bertolino, Nicola, Mandelli, Maria Luisa, Visintin, Eleonora, Bruzzone, Maria Grazia, Nigri, Anna, Epifani, Francesca, Bussone, Gennaro, Chiapparini, Luisa
• Format: Journal Article
• Language: English
• Published: Malden, MA Blackwell Publishing Ltd 01.11.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Addiction; Addictions; Addictive behaviors; Adult; Biological and medical sciences; Brain; Circuits; Cortex (prefrontal); Data processing; Decision making; decision-making under risk; Dopamine; Female; Functional magnetic resonance imaging; Headache; Headache Disorders, Secondary - diagnosis; Headache Disorders, Secondary - physiopathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Headaches; Humans; Magnetic Resonance Imaging - trends; Medical sciences; medication-overuse headache; Mesencephalon; Mesencephalon - physiopathology; mesocorticolimbic dopamine circuit; Middle Aged; Migraine; Nervous system (semeiology, syndromes); Neuroimaging; Neurology; NMR; Nuclear magnetic resonance; Substantia nigra; Time Factors; Vascular diseases and vascular malformations of the nervous system; Ventral tegmentum; Withdrawal; Headache; Nervous system diseases; Dopamine; Decision making; medication-overuse headache; Midbrain; Catecholamine; Nuclear magnetic resonance imaging; Cerebral disorder; mesocorticolimbic dopamine circuit; Chemotherapy; Treatment; Pain; Addiction; Central nervous system disease; Risk factor; Neurotransmitter; Drug of abuse; decision-making under risk; Neurological disorder; Long lasting; Cerebrovascular disease; functional magnetic resonance imaging; Functional imaging; addiction
• ISSN: 0017-8748; 1526-4610; 1526-4610
• DOI: 10.1111/j.1526-4610.2012.02276.x

Objective. The primary aim of our study was to evaluate if a group of medication‐overuse headache (MOH) patients present dysfunctions in the mesocorticolimbic dopamine circuit. The secondary aim was to disentangle the role of the medication overuse and of the acute/chronic headache in determining these alterations and to investigate their persistence. Background. Several researches have suggested that MOH may belong to the spectrum of addictive behavior. Preclinical models and neuroimaging studies have consistently demonstrated that in addiction, critical long‐lasting alterations occur in the mesocorticolimbic dopamine circuit. If MOH shares some neurophysiological features with addiction, long‐lasting functional alterations of the mesocorticolimbic dopamine system related to medication overuse should be present. Methods. We collected functional magnetic resonance imaging data during the execution of a decision‐making under risk paradigm in 8 MOH patients immediately after beginning medication withdrawal, in 8 detoxified MOH patients at 6 months after beginning medication withdrawal, in 8 chronic migraine patients, and in 8 control subjects. Results. Our results revealed that MOH patients present: (1) reduced task‐related activity in the substantia nigra/ventral tegmental area complex and increased activity in the ventromedial prefrontal cortex, when compared with controls; (2) reduced activity in the substantia nigra/ventral tegmental area complex, when compared with chronic migraine patients; (3) increased activity in the ventromedial prefrontal cortex, when compared with detoxified MOH patients. Conclusion. Our study showed that MOH patients present dysfunctions in the mesocorticolimbic dopamine circuit, in particular in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental area complex. The ventromedial prefrontal cortex dysfunctions seem to be reversible and attributable to the acute/chronic headache, whereas the substantia nigra/ventral tegmental area complex dysfunctions are persistent and possibly related to medication overuse. These dysfunctions might be the expression of long‐lasting neuroadaptations related to the overuse of medications and/or a pre‐existing neurophysiological condition leading to vulnerability to medication overuse. The observed persistent dysfunctions in the midbrain dopamine suggest that MOH may share some neurophysiological features with addiction.