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.
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
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
Pharmacology & Pharmacy
Simon Akerman, Peter J. Goadsby, Marcela Romero-Reyes
Summary: This study investigates the role of PACAP-38 in modulating cranial-autonomic and trigeminovascular responses related to headaches. The findings suggest that PACAP-38 regulates headache-related cranial-autonomic and trigeminal-vascular responses via peripheral and central components of the cranial parasympathetic projection.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
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)
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
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
Fatma Hanci, Yasemin Baranoglu Kilinc, Erkan Kilinc, Sevim Turay, Mustafa Dilek, Nimet Kabakus
Summary: The study found that plasma levels of PACAP-38 and vasoactive intestinal peptide were higher in pediatric migraine patients compared to controls, while levels of calcitonin gene-related peptide and substance P remained unchanged. No significant difference in neuropeptide levels was found between attack and attack-free periods.
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)
Review
Physiology
Florian Frank, Katharina Kaltseis, Vera Filippi, Gregor Broessner
Summary: Experimental models of human diseases are crucial for understanding and treating migraines and other headaches. Hypoxia has been found to play a significant role in these conditions, but the specific mechanisms are still unknown. Controlled normobaric hypoxia has been shown to trigger migraine attacks, and increased levels of calcitonin gene-related peptide (CGRP) have been observed during hypoxic challenges in migraine patients. Additionally, hypoxia can induce cortical spreading depression, a phenomenon associated with aura. Therefore, further research on the role of hypoxia in headaches is important for the headache community.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Clinical Neurology
Eleonora De Matteis, Valeria Caponnetto, Alfonsina Casalena, Ilaria Frattale, Amleto Gabriele, Giannapia Affaitati, Maria Adele Giamberardino, Maurizio Maddestra, Stefano Viola, Francesca Pistoia, Simona Sacco, Raffaele Ornello
Summary: Patients with migraine who experience cranial autonomic symptoms (CAS) during attacks may have a higher trigeminovascular activation than those without CAS. This study found that CAS was associated with a better response to anti-CGRP monoclonal antibody treatments.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Rapuru Rushendran, Vellapandian Chitra, Kaliappan Ilango
Summary: This study aims to identify reliable targets for migraine treatment. It identifies biomarkers such as CGRP, PACAP, NLRP3, Serotonin, and others that are involved in migraine attacks, suggesting they could be potential targets for drug development. Current medications provide temporary relief but have serious side effects. Further research, especially using natural biomarkers, is recommended to explore better treatment options for migraines through a Network Pharmacological approach.
CURRENT NEUROVASCULAR RESEARCH
(2023)
Article
Dermatology
Nita Katarina Frifelt Wienholtz, Casper Emil Christensen, Hande Coskun, Ditte Georgina Zhang, Hashmat Ghanizada, Alexander Egeberg, Jacob P. Thyssen, Messoud Ashina
Summary: This study investigated the effects of PACAP38 and a 5-HT1B/1D receptor agonist on rosacea features. It was found that sumatriptan could reduce PACAP38-induced facial skin blood flow, arterial dilation, flushing, and facial edema, suggesting a potential role for PACAP38 in rosacea pathogenesis. Further research is needed to explore the possibility of PACAP38 inhibition improving rosacea symptoms.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Review
Clinical Neurology
Roberto De Simone, Mattia Sansone, Cinzia Russo, Angelo Miele, Antonio Stornaiuolo, Simone Braca
Summary: This paper reviews the possible role of the trigemino-vascular system in maintaining cerebral perfusion pressure, and explains a migraine attack as a response to cerebral hypoxia to restore cerebral fluid balance.
NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dora Szabo, Zsolt Sarszegi, Beata Polgar, Eva Saghy, Adam Nemeth, Dora Reglodi, Andras Makkos, Aniko Gorbe, Zsuzsanna Helyes, Peter Ferdinandy, Robert Herczeg, Attila Gyenesei, Attila Cziraki, Andrea Tamas
Summary: The study found significant changes in levels of PACAP in both the porcine MI model and STEMI patients, indicating a potential regulatory role in myocardial infarction due to its cardioprotective effects. PACAP could potentially serve as a biomarker or drug target for MI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Anne Francke Christensen, Ann-Louise Esserlind, Thomas Werge, Hreinn Stefansson, Kari Stefansson, Jes Olesen
Editorial Material
Clinical Neurology
Jes Olesen
Article
Clinical Neurology
S. Guo, A. -L. Esserlind, Z. Andersson, A. L. Frederiksen, J. Olesen, J. Vissing, M. Ashina
EUROPEAN JOURNAL OF NEUROLOGY
(2016)
Review
Biology
Michael K. Borregaard, Isabel R. Amorim, Paulo A. V. Borges, Juliano S. Cabral, Jose M. Fernandez-Palacios, Richard Field, Lawrence R. Heaney, Holger Kreft, Thomas J. Matthews, Jens M. Olesen, Jonathan Price, Francois Rigal, Manuel J. Steinbauer, Konstantinos A. Triantis, Luis Valente, Patrick Weigelt, Robert J. Whittaker
BIOLOGICAL REVIEWS
(2017)
Article
Clinical Neurology
Song Guo, Anne Luise Haulund Vollesen, Rikke Dyhr Hansen, Ann-Louise Esserlind, Faisal Mohammed Amin, Anne Francke Christensen, Jes Olesen, Messoud Ashina
Article
Clinical Neurology
Song Guo, Anne Luise Haulund Vollesen, Young Bae Lee Hansen, Erik Frandsen, Malene Rohr Andersen, Faisal Mohammad Amin, Jan Fahrenkrug, Jes Olesen, Messoud Ashina
Article
Clinical Neurology
Emma Katrine Hansen, Jes Olesen
Article
Clinical Neurology
Elena R. Lebedeva, Natalia R. Kobzeva, Denis V. Gilev, Jes Olesen
Article
Clinical Neurology
Song Guo, Anne Francke Christensen, Marie Louise Liu, Benjamin Naveed Janjooa, Jes Olesen, Messoud Ashina
Article
Multidisciplinary Sciences
Sara Hougaard Pedersen, Lasse Maretty, Roshni Ramachandran, Jonas Andreas Sibbesen, Victor Yakimov, Rikke Elgaard-Christensen, Thomas Folkmann Hansen, Anders Krogh, Jes Olesen, Inger Jansen-Olesen
Article
Ecology
Serguei Saavedra, Rudolf P. Rohr, Jens M. Olesen, Jordi Bascompte
ECOLOGY AND EVOLUTION
(2016)
Article
Pharmacology & Pharmacy
Sarah L. T. Christensen, Steffen Petersen, Dorte B. Sorensen, Jes Olesena, Inger Jansen-Olesen
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2016)
Article
Clinical Neurology
Katrine Falkenberg, Jes Olesen
JOURNAL OF HEADACHE AND PAIN
(2018)
Article
Clinical Neurology
Jacob Worm, Katrine Falkenberg, Jes Olesen
JOURNAL OF HEADACHE AND PAIN
(2019)
Editorial Material
Clinical Neurology
Jes Olesen, Messoud Ashina
NATURE REVIEWS NEUROLOGY
(2019)