Conflict of Interest: None.
In Medication-Overuse Headache, fMRI Shows Long-Lasting Dysfunction in Midbrain Areas
Article first published online: 23 OCT 2012
© 2012 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 52, Issue 10, pages 1520–1534, November/December 2012
How to Cite
Ferraro, S., Grazzi, L., Muffatti, R., Nava, S., Ghielmetti, F., Bertolino, N., Mandelli, M. L., Visintin, E., Bruzzone, M. G., Nigri, A., Epifani, F., Bussone, G. and Chiapparini, L. (2012), In Medication-Overuse Headache, fMRI Shows Long-Lasting Dysfunction in Midbrain Areas. Headache: The Journal of Head and Face Pain, 52: 1520–1534. doi: 10.1111/j.1526-4610.2012.02276.x
Disclosure information: We declare that no financial support was provided by any company whose products may be related to the topic of this manuscript.
- Issue published online: 15 NOV 2012
- Article first published online: 23 OCT 2012
- Manuscript Accepted: 19 AUG 2012
- functional magnetic resonance imaging;
- medication-overuse headache;
- mesocorticolimbic dopamine circuit;
- decision-making under risk
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.
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.
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.
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.
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.