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Cells Sep 2022Migraine is a complex and debilitating disorder that is broadly recognised by its characteristic headache. However, given the wide array of clinical presentations in... (Review)
Review
Migraine is a complex and debilitating disorder that is broadly recognised by its characteristic headache. However, given the wide array of clinical presentations in migraineurs, the headache might not represent the main troublesome symptom and it can even go unnoticed. Understanding migraines exclusively as a pain process is simplistic and certainly hinders management. We describe the mechanisms behind some of the most disabling associated symptoms of migraine, including the relationship between the central and peripheral processes that take part in nausea, osmophobia, phonophobia, vertigo and allodynia. The rationale for the efficacy of the current therapeutic arsenal is also depicted in this article. The associated symptoms to migraine, apart from the painful component, are frequent, under-recognised and can be more deleterious than the headache itself. The clinical anamnesis of a headache patient should enquire about the associated symptoms, and treatment should be considered and individualised. Acknowledging the associated symptoms as a fundamental part of migraine has permitted a deeper and more coherent comprehension of the pathophysiology of migraine.
Topics: Headache; Humans; Hyperalgesia; Migraine Disorders; Pain
PubMed: 36078174
DOI: 10.3390/cells11172767 -
Biomedicine & Pharmacotherapy =... Jul 2021Migraine is a neurological ailment that is characterized by severe throbbing unilateral headache and associated with nausea, photophobia, phonophobia and vomiting. A... (Review)
Review
Migraine is a neurological ailment that is characterized by severe throbbing unilateral headache and associated with nausea, photophobia, phonophobia and vomiting. A full and clear mechanism of the pathogenesis of migraine, though studied extensively, has not been established yet. The current available information indicates an intracranial network activation that culminates in the sensitization of the trigemino-vascular system, release of inflammatory markers, and initiation of meningeal-like inflammatory reaction that is sensed as headache. Genetic factors might play a significant role in deciding an individual's susceptibility to migraine. Twin studies have revealed that a single gene polymorphism can lead to migraine in individuals with a monogenic migraine disorder. In this review, we describe recent advancements in the genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. We also discuss the potential roles of genetic and abnormal factors, including some of the metabolic triggering factors that result in migraine attacks. This review will help to accumulate current knowledge about migraine and understanding of its pathophysiology, and provides up-to-date prevention strategies.
Topics: Animals; Genetics; Humans; Inflammation; Migraine Disorders; Polymorphism, Single Nucleotide
PubMed: 34243621
DOI: 10.1016/j.biopha.2021.111557 -
Biological Trace Element Research Aug 2020Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head... (Review)
Review
Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery.
Topics: Humans; Magnesium; Magnesium Deficiency; Migraine Disorders
PubMed: 31691193
DOI: 10.1007/s12011-019-01931-z -
Seminars in Neurology Feb 2020Vestibular migraine (VM), also known as migrainous vertigo or migraine-associated vertigo, is characterized by recurrent vestibular attacks often accompanied by migraine... (Review)
Review
Vestibular migraine (VM), also known as migrainous vertigo or migraine-associated vertigo, is characterized by recurrent vestibular attacks often accompanied by migraine headaches and other migraine symptoms. It is one of the most common presenting complaints to physicians in primary care, otolaryngology, and neurology. Epidemiologic data suggest that VM may affect 1 to 3% of the general population and 10 to 30% of patients seeking treatment for dizziness. Attacks typically last minutes to hours and range from spontaneous and positional vertigo to extreme sensitivity to self and surround motion. As with headaches, nausea, and vomiting, phonophobia and photophobia are common accompanying symptoms. The clinical spectrum of VM and its underlying pathophysiological mechanisms are just being identified, with much debate about the causal relationship of vestibular symptoms and headache, no evidence-based guidelines for clinical management, limited characterization of its disease burden, and little information about its negative impact on health-related quality of life.
Topics: Humans; Migraine Disorders; Vertigo
PubMed: 31935766
DOI: 10.1055/s-0039-3402735 -
Current Pain and Headache Reports Jul 2022We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine... (Review)
Review
PURPOSE OF REVIEW
We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine epidemiology in the context of sex and gender, differences in symptomatology, and the influence of sex hormones on migraine pathophysiology (including CGRP). In part 2, we focus on practical clinical considerations for sex and gender in episodic migraine by addressing menstrual migraine and the controversial topic of hormone-containing therapies. We make note of data applicable to gender minority populations, when available, and summarize knowledge on gender affirming hormone therapy and migraine management in transgender individuals. Finally, we briefly address health disparities, socioeconomic considerations, and research bias.
RECENT FINDINGS
Migraine is known to be more prevalent, frequent, and disabling in women. There are also differences in migraine co-morbidities and symptomatology. For instance, women are likely to experience more migraine associated symptoms such as nausea, photophobia, and phonophobia. Migraine pathophysiology is influenced by sex hormones, e.g., estrogen withdrawal as a known trigger for migraine. Other hormones such as progesterone and testosterone are less well studied. Relationships between CGRP (the target of new acute and preventive migraine treatments) and sex hormones have been established with both animal and human model studies. The natural course of migraine throughout the lifetime suggests a contribution from hormonal changes, from puberty to pregnancy to menopause/post-menopause. Treatment of menstrual migraine and the use of hormone-containing therapies remains controversial. Re-evaluation of the data reveals that stroke risk is an estrogen dose- and aura frequency-dependent phenomenon. There are limited data on episodic migraine in gender minorities. Gender affirming hormone therapy may be associated with a change in migraine and unique risks (including ischemic stroke with high dose estrogen). There are key differences in migraine epidemiology and symptomatology, thought to be driven at least in part by sex hormones which influence migraine pathophysiology and the natural course of migraine throughout the lifetime. More effective and specific treatments for menstrual migraine are needed. A careful examination of the data on estrogen and stroke risk suggests a nuanced approach to the issue of estrogen-containing contraception and hormone replacement therapy is warranted. Our understanding of sex and gender is evolving, with limited but growing research on the relationship between gender affirming therapy and migraine, and treatment considerations for transgender people with migraine.
Topics: Calcitonin Gene-Related Peptide; Estrogens; Female; Gonadal Steroid Hormones; Humans; Male; Menopause; Migraine Disorders; Pregnancy; Stroke
PubMed: 35679008
DOI: 10.1007/s11916-022-01052-8 -
The New England Journal of Medicine Dec 2019Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment.
METHODS
We conducted a randomized trial to evaluate the efficacy, safety, and side-effect profile of ubrogepant. We assigned adults with migraine, with or without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant at a dose of 50 mg, or ubrogepant at a dose of 100 mg for treatment of a single migraine attack, with the option to take a second dose. The coprimary efficacy end points were freedom from pain at 2 hours after the initial dose and absence of the most bothersome migraine-associated symptom at 2 hours. Secondary end points included pain relief (at 2 hours), sustained pain relief (from 2 to 24 hours), sustained freedom from pain (from 2 to 24 hours), and absence of symptoms associated with migraine (photophobia, phonophobia, and nausea) at 2 hours.
RESULTS
A total of 1672 participants were enrolled; 559 were assigned to receive placebo, 556 to receive 50 mg of ubrogepant, and 557 to receive 100 mg of ubrogepant. The percentage of participants who had freedom from pain at 2 hours was 11.8% in the placebo group, 19.2% in the 50-mg ubrogepant group (P = 0.002, adjusted for multiplicity, for the comparison with placebo), and 21.2% in the 100-mg ubrogepant group (P<0.001). The percentage of participants who had freedom from the most bothersome symptom at 2 hours was 27.8% in the placebo group, 38.6% in the 50-mg ubrogepant group (P = 0.002), and 37.7% in the 100-mg ubrogepant group (P = 0.002). Adverse events within 48 hours after the initial or optional second dose were reported in 12.8% of participants in the placebo group, in 9.4% in the 50-mg ubrogepant group, and in 16.3% in the 100-mg ubrogepant group. The most common adverse events were nausea, somnolence, and dry mouth (reported in 0.4 to 4.1%); these events were more frequent in the 100-mg ubrogepant group (reported in 2.1 to 4.1%). Serious adverse events reported within 30 days in the ubrogepant groups included appendicitis, spontaneous abortion, pericardial effusion, and seizure; none of the events occurred within 48 hours after the dose.
CONCLUSIONS
A higher percentage of participants who received ubrogepant than of those who received placebo had freedom from pain and absence of the most bothersome symptom at 2 hours after the dose. The most commonly reported adverse events were nausea, somnolence, and dry mouth. Further trials are needed to determine the durability and safety of ubrogepant for acute migraine treatment and to compare it with other drugs for migraine. (Funded by Allergan; ClinicalTrials.gov number, NCT02828020.).
Topics: Adult; Calcitonin Gene-Related Peptide Receptor Antagonists; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperacusis; Kaplan-Meier Estimate; Male; Migraine Disorders; Nausea; Pain Management; Photophobia; Pyridines; Pyrroles
PubMed: 31800988
DOI: 10.1056/NEJMoa1813049 -
Best Practice & Research. Clinical... Feb 2024Cervicogenic headache, described almost 100 years ago, only had its clinical awakening at the end of the century with the work of Professor Sjaastad. Its classic... (Review)
Review
Cervicogenic headache, described almost 100 years ago, only had its clinical awakening at the end of the century with the work of Professor Sjaastad. Its classic definition is the induction of trigeminal symptoms from cervical disorders, thanks to trigeminocervical convergence mechanisms. For this reason, it can manifest several features typical of migraine, leading to diagnostic errors. Classically, subjects complain of fixed unilateral headaches, with cervical onset and trigeminal irradiation, associated with reduced neck mobility and flexion strength. The headache is mild to moderate, described as pulsatile or compressive, accompanied by nausea, vomiting, photophobia, phonophobia, and may present autonomic symptoms and dizziness. The pain duration varies from one day to weeks, and its frequency is unpredictable. A history of whiplash injury is common. The differential diagnosis encompasses migraine and tension-type headache. Management includes physiotherapy rehabilitation, anesthetic blocks, and selectively surgical procedures. In this article, all these aspects were extensively covered.
PubMed: 38388233
DOI: 10.1016/j.berh.2024.101931 -
Pharmacology & Therapeutics Jul 2020Migraine is a highly disabling neurovascular disorder characterized by a severe headache (associated with nausea, photophobia and/or phonophobia), and trigeminovascular... (Review)
Review
Migraine is a highly disabling neurovascular disorder characterized by a severe headache (associated with nausea, photophobia and/or phonophobia), and trigeminovascular system activation involving the release of calcitonin-gene related peptide (CGRP). Novel anti-migraine drugs target CGRP signaling through either stimulation of 5-HT receptors on trigeminovascular nerves (resulting in inhibition of CGRP release) or direct blockade of CGRP or its receptor. Lasmiditan is a highly selective 5-HT receptor agonist and, unlike the triptans, is devoid of vasoconstrictive properties, allowing its use in patients with cardiovascular risk. Since lasmiditan can actively penetrate the blood-brain barrier, central therapeutic as well as side effects mediated by 5-HT receptor activation should be further investigated. Other novel anti-migraine drugs target CGRP signaling directly. This neuropeptide can be targeted by the monoclonal antibodies eptinezumab, fremanezumab and galcanezumab, or by CGRP-neutralizing L-aptamers called Spiegelmers. The CGRP receptor can be targeted by the monoclonal antibody erenumab, or by small-molecule antagonists called gepants. Currently, rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis. Of these drugs targeting CGRP signaling directly, eptinezumab, erenumab, fremanezumab, galcanezumab, rimegepant and ubrogepant have been approved for clinical use, while atogepant is in the last stage before approval. Although all of these drugs seem highly promising for migraine treatment, their safety should be investigated in the long-term. Moreover, the exact mechanism(s) of action of these drugs need to be elucidated further, to increase both safety and efficacy and to increase the number of responders to the different treatments, so that all migraine patients can satisfactorily be treated.
Topics: Animals; Antibodies, Monoclonal; Calcitonin Gene-Related Peptide; Drug Development; Humans; Migraine Disorders; Receptors, Calcitonin Gene-Related Peptide; Receptors, Serotonin; Serotonin; Receptor, Serotonin, 5-HT1F
PubMed: 32173558
DOI: 10.1016/j.pharmthera.2020.107528