Breaking the medication overuse headache cycle: from nociplastic pain mechanisms to patient-centered interventions — the Junior Editorial Board vision

Medication-overuse headache (MOH) is a prevalent and disabling secondary headache disorder that arises in individuals with a pre-existing primary headache as a consequence of regular overuse of acute medications. Increasing evidence suggests that MOH shares fundamental pathophysiological and behavioural features with nociplastic pain conditions, supporting the view that it cannot be explained solely as a pharmacological complication. Rather, MOH appears to reflect complex interactions between neurobiological vulnerability, maladaptive neuroplasticity, and behavioural factors. In this review, we reappraise MOH through the lens of nociplastic pain to provide a unifying framework for its pathophysiology and management. Evidence from neuroimaging, neurophysiological, genetic, and experimental studies consistently indicates that MOH is associated with central sensitization, impaired descending pain modulation, and dysfunction of reward and cognitive control networks, particularly involving fronto-striatal and brainstem circuits. These alterations closely resemble those observed in other nociplastic pain conditions and appear largely reversible following successful withdrawal and preventive treatment. Behavioural features such as craving, impulsivity, catastrophizing, and cephalalgiophobia play a pivotal role in maintaining medication overuse and predicting poor outcomes, reinforcing the conceptualization of MOH as a biobehavioural syndrome. Management strategies have evolved from detoxification-centered approaches toward integrated, patient-centered care. While withdrawal remains a cornerstone of treatment, growing evidence supports flexible strategies in which preventive therapies, especially CGRP-targeting monoclonal antibodies and gepants, can be initiated before or alongside withdrawal, reducing headache burden and facilitating disengagement from acute medication overuse. Behavioural and psychological interventions, including cognitive behavioural therapy and mindfulness-based approaches, are essential to address emotional drivers, enhance adherence, and modulate nociplastic mechanisms. Current guidelines increasingly endorse multimodal and multidisciplinary management, although evidence quality remains heterogeneous. Reframing MOH within a nociplastic pain framework supports a shift from rigid detoxification models toward personalized, mechanism-based, and multidisciplinary care. Future research integrating clinical, imaging, neurobiological, and behavioural markers, potentially supported by artificial intelligence–based predictive models, may further refine patient stratification and optimize long-term outcomes in MOH.