Review
Medicine, General & Internal
Matilde Capi, Valerio De Angelis, Donatella De Bernardini, Ottavia De Luca, Fabiola Cipolla, Luana Lionetto, Maurizio Simmaco, Paolo Martelletti
Summary: The discovery of CGRP's role in migraine pathophysiology has led to the development of new drugs, showing potential to transform migraine management, although its exact position is yet to be determined.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Physiology
Peter Holzer, Ulrike Holzer-Petsche
Summary: The development of small-molecule CGRP receptor antagonists and monoclonal antibodies targeting the CGRP system has revolutionized migraine management. However, constipation has been observed as a major adverse event in patients treated with these therapies. This review article investigates the mechanism behind CGRP inhibition-induced constipation.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Medicine, General & Internal
Lars Edvinsson
Summary: Migraine is a common neurovascular disorder, affecting over 15% of the global population. Women are three times more likely to suffer from migraine compared to men. The underlying mechanisms of migraine are still largely unknown, but molecules such as CGRP play a crucial role in its pathophysiology.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Anesthesiology
David A. C. Messerer, Thomas Datzmann, Anke Baranowsky, Leandra Peschel, Andrea Hoffmann, Michael Groeger, Michael Amling, Martin Wepler, Benedikt L. Nussbaum, Shan Jiang, Paul Knapstein, Antonia Donat, Enrico Calzia, Peter Radermacher, Johannes Keller
Summary: The study found that CGRP receptor antagonism with olcegepant was not beneficial in a porcine model of polymicrobial sepsis, which closely mimics human sepsis.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Clinical Neurology
Justin L. Hoskin, Terry D. Fife
Summary: The CGRP medications appear to be a decent treatment option for vestibular migraine (VM), with most patients experiencing some level of symptom improvement.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Francesca Puledda, Elisa Martins Silva, Kanokrat Suwanlaong, Peter J. Goadsby
Summary: Migraine is a common neurological disorder with complex neurobiology, affecting both central and peripheral nervous systems. Recent advancements in understanding its pathophysiology have led to the development of novel treatments, which are changing the clinical approach to the disease globally.
JOURNAL OF NEUROLOGY
(2023)
Review
Immunology
Sandhya Jinesh
Summary: Migraine is a common neurological disorder with a significant socio-economic impact. CGRP plays a key role in triggering migraines by causing vasodilation in extracerebral arteries. While there are various medications used for migraine prevention and treatment, targeted therapies are limited. CGRP receptor inhibitors have been developed as drugs for migraine therapy, and a risk-benefit comparison of different classes of these inhibitors is provided in this review article.
INFLAMMOPHARMACOLOGY
(2023)
Review
Immunology
Mahsa Bagherzadeh-Fard, Mohammad Amin Yazdanifar, Mona Sadeghalvad, Nima Rezaei
Summary: Objective: The objective of this systematic review is to demonstrate the effectiveness of Erenumab in preventing episodic and chronic migraines, which is still being researched. Background: Migraine is a chronic neurovascular disorder that causes disability and societal burden. Existing medications for migraine prevention often have undesirable side effects and limited efficacy. Erenumab, a monoclonal antibody targeting calcitonin gene-related peptide receptors, has recently been approved by the FDA for migraine prevention. Methods: A systematic review was conducted using Scopus and PubMed databases, searching for articles from 2016 to March 18, 2022, with keywords Erenumab or AMG 334 and migraine. Results: Out of 605 papers, 53 were eligible for investigation. Erenumab at dosages of 70 mg and 140 mg showed a reduction in monthly migraine days and acute migraine-specific medication days. It also demonstrated high rates of reduction in monthly migraine days from the baseline in different regions. Erenumab was effective from the first week of administration and throughout the treatment period. It also showed efficacy in treating migraines with allodynia, aura, prior preventive therapy failure, medication overuse headache, and menstrual migraine. Combination therapy with other preventive drugs, such as Onabotulinumtoxin-A, yielded favorable outcomes. Conclusion: Erenumab exhibited remarkable efficacy in both short-term and long-term treatment of episodic and chronic migraines, especially in patients with difficult-to-treat migraine headaches.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Clinical Neurology
Stewart J. Tepper, Messoud Ashina, Uwe Reuter, Yngve Hallstroem, Gregor Broessner, Jo H. Bonner, Hernan Picard, Sunfa Cheng, Denise E. Chou, Feng Zhang, Jan Klatt, Daniel D. Mikol
Summary: The study found that treatment with erenumab in patients with migraine is associated with a significant and sustained reduction in the use of acute headache medication, particularly migraine-specific medication.
JOURNAL OF HEADACHE AND PAIN
(2021)
Article
Chemistry, Medicinal
Guanglin Luo, Xiang-Jun Jiang, Ling Chen, Charles M. Conway, Michael Gulianello, Walter Kostich, Deborah Keavy, Laura J. Signor, Ping Chen, Carl Davis, Valerie J. Whiterock, Richard Schartman, Kimberly A. Widmann, John E. Macor, Gene M. Dubowchik
Summary: Researchers identified a series of high-affinity heterocycle derivatives as CGRP receptor antagonists, some of which showed good oral exposure and reduced time-dependent CYP3A4 inhibition. However, challenges remained in improving the oral bioavailability of these compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Pharmacology & Pharmacy
Gabriella Juhasz, Kinga Gecse, Daniel Baksa
Summary: Since the introduction of the International Classification of Headache Disorders 35 years ago, we are now in the era of the second great revolution in migraine therapies. The discoveries of triptans and anti-CGRP therapies have brought breakthroughs in acute and preventive migraine treatment. In this article, the latest clinical studies and real-world data on available migraine-specific medications, as well as novel drug targets and challenges in migraine therapy, are reviewed.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Cinder Faith Cohen, Jueun Roh, Sang Hoon Lee, Chul-Kyu Park, Temugin Berta
Summary: Migraine is a neurovascular disorder affecting 12% of the global population. Research suggests that nociceptive neurons in the trigeminal ganglia play a crucial role in migraine pain signals. These neurons innervate the meninges and transmit pain signals to the thalamus. Targeting nociceptive neurons, which express transient receptor potential (TRP) channels, may be a promising approach for migraine treatment. This review discusses the role of nociceptive neurons, challenges with current drugs, and the potential of TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Simone de Vries Lentsch, Ingrid M. Garrelds, A. H. Jan Danser, Gisela M. Terwindt, Antoinette MaassenVanDenBrink
Summary: This study evaluated the serum levels of Calcitonin Gene-Related Peptide (CGRP)-like immunoreactivity (CGRP-LI) in migraine patients before and after starting treatment with erenumab, and examined their association with clinical treatment response. The results showed that lower levels of serum CGRP-LI 2-4 weeks after starting treatment with erenumab were associated with a higher reduction in migraine days after three months of treatment. This suggests that changes in CGRP levels shortly after starting erenumab are important for its clinical effect.
JOURNAL OF HEADACHE AND PAIN
(2022)
Editorial Material
Physiology
Kimberly D. Mackenzie, Mario Ortega, Yoel Kessler, Verena Ramirez Campos, Lynda J. Krasenbaum, Karen Carr, Xiaoping Ning, Jennifer Stratton
Summary: Calcitonin gene-related peptide (CGRP) pathway-targeted treatments are effective for preventing and treating migraines, but may cause constipation. However, limited data from a review article do not support the claim that constipation occurs in more than 50% of patients treated with CGRP pathway-targeted treatments.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Clinical Neurology
Simone Quintana, Marco Russo, Gian Camillo Manzoni, Paola Torelli
Summary: This observational study compares the efficacy, safety, and impact of anti-CGRP monoclonal antibodies on additional parameters such as disability in social, family, and work activities.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Isabella Mai Christiansen, Jacob C. A. Edvinsson, Philip Reducha, Lars Edvinsson, Kristian Agmund Haanes
Summary: The present study demonstrates that ACEA alone does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1.
JOURNAL OF HEADACHE AND PAIN
(2022)
Review
Physiology
Jacob C. A. Edvinsson, Kristian A. Haanes, Lars Edvinsson
Summary: This review focuses on the trigeminovascular system (TGV) and discusses the signaling between fibers, as well as the potential role of neuropeptides and their receptors in migraine pathophysiology.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Maryam Mostajeran, Lars Edvinsson, Hilda Ahnstedt, Kajsa Arkelius, Saema Ansar
Summary: This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats. The results showed that there were differences in the expression of specific proteins in different brain regions of female rats after stroke, which may be important for future therapeutic strategies.
Review
Medicine, General & Internal
Lars Edvinsson
Summary: Migraine is a common neurovascular disorder, affecting over 15% of the global population. Women are three times more likely to suffer from migraine compared to men. The underlying mechanisms of migraine are still largely unknown, but molecules such as CGRP play a crucial role in its pathophysiology.
JOURNAL OF INTERNAL MEDICINE
(2022)
Editorial Material
Clinical Neurology
Lars Edvinsson, Jacob C. A. Edvinsson, Kristian A. Haanes
Summary: The paper presents an analysis of mRNA expression in human and mouse trigeminal ganglia at single-nucleus resolution. It suggests new targets for pain therapies, but the findings should be interpreted in the context of available protein data and warrant functional verification.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Physiology
Andre Erdling, Sara Ellinor Johansson, Aneta Radziwon-Balicka, Saema Ansar, Lars Edvinsson
Summary: Ischemia causes upregulation of vasoconstrictive receptor systems in the cerebral vasculature. Focal ischemic stroke increases vascular sensitivity to UDP-beta-S, while subarachnoid hemorrhage does not.
PHYSIOLOGICAL REPORTS
(2022)
Review
Cell Biology
Philip Victor Reducha, Lars Edvinsson, Kristian Agmund Haanes
Summary: Migraines are a common neurological disorder characterized by inflammation and sensitization mechanisms, with intracranial meningeal inflammation playing a key role. Animal models have provided valuable insights into these mechanisms.
Article
Clinical Neurology
Aida Maddahi, Lars Edvinsson, Karin Warfvinge
Summary: The expression of vasopressin and its receptors in the brain and trigeminovascular system, particularly in migraine-related regions, was identified. No differences in CGRP and vasopressin expression were found between male and female rats in the trigeminal ganglion. However, the number of RAMP1, oxytocin, oxytocin receptor, and vasopressin receptors immunoreactive cells were higher in females. Vasopressin and its receptors were expressed in both hypothalamus and trigeminal ganglion, with higher levels of vasopressin mRNA in the hypothalamus. Vasopressin and closely related oxytocin may play important roles in migraine pathophysiology.
JOURNAL OF HEADACHE AND PAIN
(2022)
Article
Chemistry, Medicinal
Jesper Peter Bomers, Anne-Sofie Grell, Lars Edvinsson, Sara Ellinor Johansson, Kristian Agmund Haanes
Summary: This study investigated the effects of trametinib treatment on female rats with induced subarachnoid haemorrhage. The results showed that trametinib treatment significantly improved arterial contractility, reduced subacute increases in intracranial pressure, and improved sensorimotor and neurological outcomes in female rats.
Article
Clinical Neurology
Philip V. Reducha, Jesper P. Boemers, Lars Edvinsson, Kristian A. Haanes
Summary: This study aimed to investigate the behavioral changes similar to migraine caused by CFA application on the skull in rats, and the potential mitigating effects of the CGRP specific antibody fremanezumab after CFA application. The results showed that surgical application of CFA to the dura caused periorbital allodynia and increased CGRP positive fibers in the trigeminal ganglion. However, fremanezumab did not alleviate periorbital allodynia, although it reduced the amount of CGRP positive fibers.
FRONTIERS IN NEUROLOGY
(2023)
Editorial Material
Medicine, General & Internal
Kristian A. Haanes, Lars Edvinsson
Article
Clinical Neurology
Aida Maddahi, Karin Warfvinge, Anja Holm, Jacob C. A. Edvinsson, Philip Victor Reducha, Spyridoula Kazantzi, Kristian A. Haanes, Lars Edvinsson
Summary: This study investigated the distribution of progesterone in the trigeminovascular system and its role in modulating sensory neurotransmission. The results suggest that progesterone may modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further research is needed to fully understand the underlying mechanisms and physiological implications of these findings.
JOURNAL OF HEADACHE AND PAIN
(2023)
Article
Multidisciplinary Sciences
Lena Erlandsson, Lena Ohlsson, Zahra Masoumi, Mimmi Rehnstrom, Tina Cronqvist, Lars Edvinsson, Stefan R. Hansson
Summary: Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and organ damage. This study found that placenta-derived extracellular vesicles (STBEVs) in PE patients have negative effects on vascular contractility and cause structural damage to blood vessels. These effects can be reduced by blocking vesicle uptake. This discovery provides a new therapeutic strategy for preventing cardiovascular risks caused by PE.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Anette Sams, Kristian Agmund Haanes, Anja Holm, Spyridoula Kazantzi, Lars Friis Mikkelsen, Lars Edvinsson, Susan Brain, Majid Sheykhzade
Summary: This study characterized the vasomotor responses of isolated coronary, cerebral, and mesenteric arteries in Gottingen Minipigs (GM), and compared the responses to those obtained from parallel studies using other artery types. The results showed that different arterial sources had different responses to selected agonists of endothelial, sympathetic, parasympathetic, and sensory pathways. The study also demonstrated the robust nature of the vasomotor responses after 24 hours of cold storage of vascular tissue.
VASCULAR PHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Mimmi Rehnstrom, Hilda Ahnstedt, Diana N. Krause, Marie Louise Edvinsson, Kristian Agmund Haanes, Lars Edvinsson
Summary: This study found that sex hormones do not directly affect vasoconstrictive changes following ischemic stroke, but the loss of ovarian function does impact this process.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
