Pain Processing in Medication Overuse Headache: A Functional Magnetic Resonance Imaging (fMRI) Study

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) activitydependent 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.