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Background/Objectives : Chronic migraine with medication-overuse headache (CM-MOH) is neurophysiologically characterized by increased cortical excitability with sensitization at both the thalamocortical and the cortical levels. It is unclear whether the increased cortical excitability could be reverted by medication withdrawal (i.e., brain state) or whether it is a brain trait of individuals predisposed to medication overuse. In this study, we aim to investigate whether withdrawal from overused drugs can influence and restore these neurophysiological abnormalities. Methods : Somatosensory evoked potentials (SSEPs) were elicited by electrical stimulation of the median nerve (M), the ulnar nerve (U), and the simultaneous stimulation of both nerves (MU) in 14 patients with CM-MOH before (T 0 ) and after (T 1 ) a three-week withdrawal protocol and, for comparison, in 14 healthy volunteers (HVs) of a comparable age distribution. We measured the level of thalamocortical (pre-HFO) and cortical activation (post-HFO) by analyzing the high-frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Furthermore, we calculated the habituation and the degree of cortical lateral inhibition (dLI) of N20-P25 low-frequency SSEPs. Results : After the three-week withdrawal protocol (T 1 ), we observed a normalization of the baseline habituation deficit (T 0 : +0.10 ± 0.54; T 1 : -0.53 ± 0.8; p = 0.040) and a reduction in the amplitude for both pre-HFO ( p < 0.009) and post-HFO ( p = 0.042), with values comparable to those of the HVs. However, no effects were observed on the dLI ( p = 0.141). Conclusions : Our findings showed that withdrawal from overused drugs could affect the increased excitability of the non-painful somatosensory system in patients with CM-MOH, reducing the level of sensitization at both the thalamocortical and the cortical levels.

Background/Objectives : Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods : We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analysing the amplitude of the first block (100 sweeps) and to evaluate habituation by measuring the amplitude response decrement after six blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results : There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEP parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication withdrawal. Conclusions : We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli.