OBJECTIVE: The primary aim was to investigate functional differences between medication overuse headache (MOH) patients and controls with the purpose of evaluating the presence of a global alteration in the processing of noxious stimuli throughout the pain matrix. The secondary aim was to investigate whether activations in MOH patients normalize after medication withdrawal, which would suggest a possible role of the pain matrix in headache chronification. DESIGN: Functional magnetic resonance imaging was performed during painful mechanical stimulation in nine female patients with MOH immediately and at 6 months after beginning medication withdrawal, and in nine control participants. RESULTS: Compared with controls, immediately after beginning withdrawal, the MOH patients showed reduced pain-related activity across the primary somatosensory cortex, inferior parietal lobule, and supramarginal gyrus, as well as in regions of the lateral pathway of the pain matrix. At 6 months, these differences were no longer detectable. CONCLUSION: Our findings suggest that significant functional changes occur in the lateral pain pathway in MOH patients. These could result from different processes: 1) cortical down-regulation aimed at reducing painful input to the cortex; 2) activity-dependent plasticity induced by excessive painful input during migraine attacks; and 3) direct effect of medication overuse. At 6 months after withdrawal, activity in these regions normalized, suggesting that no irreversible changes occur due to medication overuse.
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