Maassen-van-den-Brink, A. (Antoinette)

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    Prolactin and oxytocin
    (2023) Lo-Cascio, S. (Salvatore); Börner, C. (Corinna); Kodounis, M. (Michalis); Ratti, S. (Susanna); Messlinger, K. (Karl); Rivera-Mancilla, E. (Eduardo); Onan, D. (Dilara); Mikolajek, D. (David); Szewczyk, A.K. (Anna K.); Cernigliaro, F. (Federica); Aktürk, T. (Tülin); Ulutas, S. (Samiye); Vries, T. (T.) de; Ragaglini, C. (Chiara); Al-Hassany, L. (Linda); Tsanoula, S. (Sofia); Maassen-van-den-Brink, A. (Antoinette); Villino, R. (Rafael)
    Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development.
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    European headache federation consensus on the definition of resistant and refractory migraine
    (2020) Pozo-Rosich, P. (Patricia); Ducros, A. (Anne); Martelletti, P. (Paolo); Reuter, U. (Uwe); Sinclair, A. (Alexandra); Ruiz-de-la-Torre, E. (Elena); Lampl, C. (Christian); Sacco, S. (Simona); Katsarava, Z. (Zaza); Braschinsky, M. (Mark); Sanchez-del-Río, M. (Margarita); Little, P. (Patrick); Maassen-van-den-Brink, A. (Antoinette)
    Introduction: Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances. Main body: Definitions were established with a consensus process using the Delphi method. Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures. Resistant migraine is defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts. Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 consecutive months. Drug failure may include lack of efficacy or lack of tolerability. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required. Conclusions: We hope, that the updated EHF definition will be able to solve the conflicts that have limited the use of definitions which have been put forward in the past. Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved. This new definition has also the aim to increase the understanding of the impact of the migraine as a disease with all of its social, legal and healthcare implications. It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.