Article
Biochemistry & Molecular Biology
Zoe Tasma, Andrew Siow, Paul W. R. Harris, Margaret A. Brimble, Simon J. O'Carroll, Debbie L. Hay, Christopher S. Walker
Summary: This study validated commercially available antibodies and used them to detect PACAP-responsive receptors in the trigeminal ganglia. Antibodies that could differentiate between receptor splice variants were identified, and expression of multiple receptors in neuronal and glial-like cells was observed. These findings suggest that these receptors are potential targets for migraine treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Charlotte Ernstsen, Sarah L. Christensen, Rikke H. Rasmussen, Brian S. Nielsen, Inger Jansen-Olesen, Jes Olesen, David M. Kristensen
Summary: Using in vivo and ex vivo models, the study shows that PACAP-38 can provoke migraine-like changes independently of CGRP and partially through K-ATP channels. The findings suggest that PACAP-38 antagonism could be a potential alternative therapeutic approach for patients non-responsive to CGRP-targeting therapies.
Review
Clinical Neurology
Vinita M. Mistry, Paige L. Morizio, Marc J. Pepin, William E. Bryan, Jamie N. Brown
Summary: The systematic review evaluated the efficacy and safety of memantine for prophylactic treatment of episodic migraine, showing potential benefit in reducing migraine days and headache severity. Additional long-term studies using active comparators are needed to further clarify the role of memantine in migraine treatment.
Article
Neurosciences
Adisa Kuburas, Bianca N. Mason, Benjamin Hing, Anne-Sophie Wattiez, Alyssa S. Reis, Levi P. Sowers, Cristina Moldovan Loomis, Leon F. Garcia-Martinez, Andrew F. Russo
Summary: CGRP and PACAP have emerged as mediators of migraine, inducing migraine-like symptoms through independent pathways in mice. Monoclonal antibodies targeting PACAP may be effective in patients unresponsive to CGRP-based therapeutics.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Behavioral Sciences
Chuan Hu, Yixin Zhang, Ge Tan
Summary: Topiramate has been proven effective for migraine prevention in North America and Europe, but is still considered an off-label medication for migraine treatment in China due to limited evidence. This review summarizes the effects of topiramate on migraine patients in China, providing reference for Chinese doctors.
BRAIN AND BEHAVIOR
(2021)
Review
Neurosciences
Song Guo, Inger Jansen-Olesen, Jes Olesen, Sarah Louise Christensen
Summary: Migraine is a widespread and debilitating neurological condition affecting more than a billion people worldwide. The recent introduction of monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) has been a significant advance in migraine therapy. However, a large proportion of patients are unresponsive to these new drugs, and it is believed that the pituitary adenylate cyclase-activating peptide (PACAP) pathway may be involved in these cases.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Camila Naegeli Caverni, Aline Turbino da Costa, Caio Grava Simioni, Rosemeire Rocha Fukue, Celia Harumi Tengan, Thais Rodrigues Villa
Summary: The study indicates that topiramate is effective in treating chronic migraine patients by reducing pain and weight, and increasing fat-free mass. This effect is more prominent in obese patients, suggesting potential benefits in managing chronic migraine for this population.
Review
Pharmacology & Pharmacy
William David Wells-Gatnik, Tiffany Yazmin Wences Chirino, Fatma Nur Onan, Dilara Onan, Paolo Martelletti
Summary: This article introduces new drugs for the treatment of migraine and discusses their clinical trial outcomes. As approximately 50% of patients do not respond to calcitonin gene-related peptide therapies, there is significant value in future drug innovation. Overall, these emerging drugs are largely developed based on important targets of migraine pathogenesis, but the clinical value of individual drugs needs further research to appropriately target the relevant pathways.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Article
Behavioral Sciences
Michael Nsaka, Armin Scheffler, Sebastian Wurthmann, Hannah Schenk, Christoph Kleinschnitz, Martin Glas, Dagny Holle
Summary: The study found that a mandatory break in CGRP (pathway) monoclonal antibody therapy had a negative short-term impact on migraine patients, leading to an increase in the number of migraine days and the use of acute medications.
BRAIN AND BEHAVIOR
(2022)
Article
Oncology
Oana C. C. Danciu, Matthias Holdhoff, Richard A. A. Peterson, James H. H. Fischer, Li C. C. Liu, Heng Wang, Neeta K. K. Venepalli, Rozina Chowdhery, M. Kelly Nicholas, Meredith J. J. Russell, Timothy M. M. Fan, Paul J. J. Hergenrother, Theodore M. M. Tarasow, Arkadiusz Z. Z. Dudek
Summary: This study is the first-in-human clinical trial of PAC-1, assessing its maximum tolerated dose, safety, and pharmacokinetics. The recommended phase 2 dose of PAC-1 was found to be 750 mg/day. The study also observed clinical activity of PAC-1 in patients with neuroendocrine tumors, suggesting further investigation is warranted.
BRITISH JOURNAL OF CANCER
(2023)
Article
Clinical Neurology
Stefan Evers, Achim Frese, Oliver Summ, Ingo W. Husstedt, Martin Marziniak
Summary: The study evaluated the efficacy and tolerability of levetiracetam as a prophylactic treatment for episodic migraine. The results showed that levetiracetam has some potential in the treatment of episodic migraine, but it is not superior to other anticonvulsant drugs. Levetiracetam showed better efficacy in patients with migraine with aura and in less affected migraine patients.
Review
Clinical Neurology
Adisa Kuburas, Andrew F. Russo
Summary: The neuropeptides CGRP and PACAP play important roles in migraine pathogenesis by causing vasodilation and migraine-like symptoms. They have similarities in their clinical and preclinical actions, but also notable differences, such as PACAP causing premonitory-like symptoms and CGRP and PACAP being found in different ganglia. Both peptides cause similar migraine-like symptoms in rodents, but may act through independent mechanisms. The existence of multiple receptors for CGRP and PACAP further complicates the signaling pathways involved, suggesting that targeting PACAP receptors could complement current CGRP-based migraine therapeutics.
JOURNAL OF HEADACHE AND PAIN
(2023)
Article
Pharmacology & Pharmacy
Zoe Tasma, Andrew Siow, Paul W. R. Harris, Margaret A. Brimble, Debbie L. Hay, Christopher S. Walker
Summary: The PACAP-responsive receptors exhibit varied pharmacological profiles but activate signaling in a similar manner. The PAC(1s) receptor can act as a dual receptor for VIP and PACAP. The effectiveness of blocking a signaling pathway can be influenced by the endogenous PACAP family agonist present, with PACAP-38 showing less antagonism compared to PACAP-27 and VIP.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
Lily Zhang, Yanjie Zhou, Liu Yang, Yue Wang, Zheman Xiao
Summary: The aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a chronic migraine (CM) model. The results showed that PACAP6-38 improved NTG-induced central sensitization by regulating synaptic plasticity in the trigeminal nucleus caudalis (TNC) of CM rat, and down-regulated the expression of the ERK/CREB/BDNF signaling pathway. These findings provide new insights into the treatments targeting PACAP/PAC1R in migraine.
JOURNAL OF HEADACHE AND PAIN
(2023)
Article
Biochemistry & Molecular Biology
Elisabeth Anne Adanma Obara, Birgitte Georg, Jens Hannibal
Summary: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a crucial role in migraine pathophysiology. We have developed a sandwich ELISA assay capable of detecting and accurately quantifying PACAP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Matteo Castaldo, Marta Waliszewska-Prosol, Maria Koutsokera, Micaela Robotti, Marcin Straburzynski, Loukia Apostolakopoulou, Mariarita Capizzi, Oneda Cibuku, Fidel Dominique Festin Ambat, Ilaria Frattale, Zukhra Gadzhieva, Erica Gallo, Anna Gryglas-Dworak, Gleni Halili, Asel Jusupova, Yana Koperskaya, Alo-Rainer Leheste, Maria Laura Manzo, Andrea Marcinno, Antonio Marino, Petr Mikulenka, Bee Eng Ong, Burcu Polat, Zvonimir Popovic, Eduardo Rivera-Mancilla, Adina Maria Roceanu, Eleonora Rollo, Marina Romozzi, Claudia Ruscitto, Fabrizio Scotto di Clemente, Sebastian Strauss, Valentina Taranta, Maria Terhart, Iryna Tychenko, Simone Vigneri, Blazej Misiak, Paolo Martelletti, Alberto Raggi
Summary: This study reviewed the incidence and characteristics of headache after COVID-19 vaccination. The results showed that the risk of developing headache doubled after vaccination, with no differences between different vaccine types. Some patients experienced pulsating headache with sensitivity to sound and light, and aggravation with activity.
JOURNAL OF HEADACHE AND PAIN
(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)
Letter
Clinical Neurology
Simone Vigneri, Valeria Bono
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.
Review
Cardiac & Cardiovascular Systems
Deborah N. Kalkman, Emile G. M. Couturier, Abdelhak El Bouziani, Jorge Dahdal, Jolien Neefs, Janneke Woudstra, Birgit Vogel, Daniela Trabattoni, Antoinette MaassenVanDenBrink, Roxana Mehran, Robbert J. de Winter, Yolande Appelman
Summary: Migraine is a chronic neurovascular disease with complex pathophysiology and multiple causes. Women are more likely to suffer from migraine, and it is the most disabling disease in women under 50 years old. Migraine with aura is associated with increased risk of cardiovascular diseases, such as stroke, atrial fibrillation, myocardial infarction, and cardiovascular death. Medications for migraine treatment may have potential risks for patients with cardiovascular disease. Further research is needed to understand the contraindications for newer treatments. This review discusses the pathophysiology, associations with cardiovascular diseases, current therapies, and future research directions.
EUROPEAN HEART JOURNAL
(2023)
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
Review
Clinical Neurology
Dimos D. Mitsikostas, Christian Waeber, Margarita Sanchez-del-Rio, Bianca Raffaelli, Hakan Ashina, Antoinette Maassen van den Brink, Anna Andreou, Patricia Pozo-Rosich, Alan Rapoport, Messoud Ashina, Michael A. Moskowitz
Summary: Migraine, a leading cause of disability in over one billion people globally, is underestimated even by those who suffer from it. Current treatments have limited efficacy and potential side effects, resulting in low treatment adherence. Recently, a new class of drugs called ditans, selective serotonin 5-HT1F receptor agonists, has been introduced to the international market. This article reviews preclinical studies from the late 1990s and recent clinical research that led to the development and approval of ditans for acute migraine treatment by the US FDA and the European Medicines Agency.
NATURE REVIEWS NEUROLOGY
(2023)
Review
Clinical Neurology
Bianca Raffaelli, Eloisa Rubio-Beltran, Soo-Jin Cho, Roberto De Icco, Alejandro Labastida-Ramirez, Dilara Onan, Raffaele Ornello, Ruth Ruscheweyh, Marta Waliszewska-Prosol, Roberta Messina, Francesca Puledda
Summary: Headache disorders are a global public health concern that affect diverse populations. There are disparities in headache service organizations and pharmacological treatment worldwide, with limited access, awareness, and economic barriers being major obstacles. Telemedicine could be a solution to improve access to headache care, especially in underserved areas. Health disparities, treatment access, and medication availability are concerning issues in headache medicine, and efforts should be made to minimize access barriers for equitable global headache care.
JOURNAL OF HEADACHE AND PAIN
(2023)
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)
Letter
Anesthesiology
Simone Vigneri, Iacopo Battaglini
CLINICAL JOURNAL OF PAIN
(2023)
Letter
Anesthesiology
Simone Vigneri, Marco La Grua, Gianfranco Sindaco, Matteo Zanella
