• Tzu-Hsien Lai and Shuu-Jiun Wang.
• Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
• Curr Pain Headache Rep. 2018 Jan 16; 22 (1): 1.

AbstractMedication overuse headache (MOH) is a secondary headache syndrome defined as the deterioration of the headache associated with the overuse of analgesics. The prevalence of MOH is 1-2% in the general population and even up to 50% in special clinics. Overuse of abortive medications is highly associated with chronic daily headaches and also a known risk factor for headache evolution. Possible mechanisms include neural plasticity changes such as sensitization and defective endogenous pain inhibition. Psychological studies have suggested dependence, even addiction, in patients with MOH. Neuroimaging studies have provided valuable information concerning MOH pathophysiology. Magnetic resonance imaging analyzed by voxel-based morphometry showed gray matter volume changes in brain areas participating the pain modulations. Changes of brain function at similar areas have been revealed by positron emission tomography and functional magnetic resonance imaging studies. Many of these changes were correlated with either headache and/or analgesics parameters such as frequency and duration. These changes are typically reversible after successful treatment. Though the cause or consequence debate remains unsettled, we are more in favor of these findings as maladaptive changes to the frequent headaches or medication overuse. Of these brain areas involved in MOH, orbitofrontal cortex is of interest in several ways. In an early positron emission tomography study, the hypometabolism persists after successful treatment which implied a causal role. The following morphological studies showed the orbitofrontal cortex volume could predict treatment responses. Functional magnetic resonance imaging studies, task positive and also resting-state ones, also reported changes within the mesocorticolimbic dopamine system, also known as reward system. Important brain areas of this system include ventral tegmental area, striatum, and orbitofrontal cortex. The system plays an important role in decision-making, dependence, and addiction, as implicated in psychological studies of MOH. Further studies on neuromodulation of this system may be considered in the treatment of MOH.

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