Migraine is a primary headache showing a multifactorial component that includes altered pain processing, psychological/emotional problems, neurocognitive and executive function deficits, all with a possible genetic association. The aim of the current study will be to evaluate the association between sensitisation, psychological/emotional, neurocognitive and genetic profile on conditioned pain modulation (CPM) in women with migraine from a multidisciplinary perspective.

A cross-sectional observational case–control study including 90 women with chronic migraine, 90 women with episodic migraine and 90 women without migraine (as controls) will be conducted. Clinical variables (disability, pain), processing (sensitisation-associated, neuropathic-like symptoms), psychological/emotional (anxiety, depression, sleep quality, catastrophising), neurocognitive (attention), executive functions (memory, mental inhibition, speed processing) and genetics (Val158Met polymorphism rs4680 gene) will be assessed in all subjects by healthcare professionals. Subsequently, CPM will be evaluated with the cold-pressor test paradigm by assessing changes obtained in mechanical and thermal stimuli. The association of each group of variables on CPM will be analysed with multivariate analyses (OMNIBUS analysis of variance). A network model will also be created to identify those variables showing the greatest key measure of centrality with the rest of the severity indicators (strength, intermediation and closeness) to establish the potentially therapeutic targets in patients with migraine from a multidisciplinary point of view.

The protocol of the current study has been approved by the Ethics Committee of all involved institutions (Hospital Universitario Fundación Alcorcón 24–117, Universidad Rey Juan Carlos 010220240912024). All procedures will be conducted following the Declaration of Helsinki. Participants will be informed of the aims and procedures of the study and will receive the informed written consent which should be signed before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.