Headache Series editors Paolo Martelletti Roma, Italy Rigmor Jensen Glostrup, Denmark
The huge importance of headache in public health arises from its causal association with personal and societal burdens of pain, disability, damaged quality of life, and financial costs. Headache disorders are in fact common and ubiquitous. They have a neurological basis, but rarely they are due to serious underlying illness. The primary headache disorders migraine, tension-type headache, and cluster headache are easily seen by family physicians or GPs; however, a relatively small number of secondary headache disorders could also be encountered in primary care. It is important that they are recognized and treated in the most appropriate way because of their potentially dangerous underlying causes; moreover, mismanagement and overuse of medications to treat acute headache are major risk factors for disease aggravation. Purpose of this Series, endorsed by the European Headache Federation EHF, is to provide a detailed description of all aspects of headache disorders that are common and relevant both in primary care and in hospital setting. More information about this series at http://www.springer.com/series/11801
Messoud Ashina Pierangelo Geppetti Editors Pathophysiology of Headaches From Molecule to Man
Editors Messoud Ashina, MD, PhD, DMSc Professor of Neurology Department of Neurology Danish Headache Center Rigshospitalet and Glostrup Hospital Glostrup Denmark Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Pierangelo Geppetti, MD Professor of Clinical Pharmacology Department of Health Sciences University of Florence Florence Italy Head, Headache Center University Hospital Careggi Florence Italy ISSN 2197-652X ISSN 2197-6538 (electronic) Headache ISBN 978-3-319-15620-0 ISBN 978-3-319-15621-7 (ebook) DOI 10.1007/978-3-319-15621-7 Library of Congress Control Number: 2015936082 Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com)
Foreword The Headache Series is enhanced by this second volume, edited by Messoud Ashina and Pierangelo Geppetti, both well-known scientists in the headache pathophysiology area, to whom a delicate task has been assigned: to render the most updated picture of pathophysiology of headache disorders involving all the many prestigious actors who dominate the scenes of this shimmering theatre. Their different disciplinary backgrounds, primarily neurology but also pharmacology, guaranteed a combined-vision, factual planning of this important chapter in Headache Medicine. The operation has been brilliantly carried out and the completeness of the volume is now in front of the readers eyes and is available indiscriminately to everyone with a clinical-scientific-educational interest towards Headache Medicine. The European Headache Federation thanks the Editors for their essential contribution to this complex and fine volume and every author of each chapter for playing an important role in spreading headache culture through the medical world. The education/dissemination path within the EHF project of the Headache Series has concluded its second important step. Paolo Martelletti Sapienza University, Rome, Italy Rigmor Høiland Jensen University of Copenhagen, Copenhagen, Denmark v
Preface The purpose of the second Headache Series book endorsed by the European Headache Federation is to bring together in one book much of the diverse body of work on the pathophysiology of headaches. We hoped to provide the reader with recent advances in the pathophysiology of migraine, cluster headache, and tension-type headache. The topics we have chosen for the book should be of interest to headache basic and clinical science researchers as well as researchers in the pharmaceutical industry. We also believe that this book will also be attractive to senior undergraduate and graduate students in the health sciences, whose interests include headache. The book is organized into an introductory chapter on the anatomy of headache, which is essential to understand the pathophysiology of headaches, followed by topical chapters focusing on animal and human models, genetics, imaging, neurophysiology, and biochemistry. We also asked experts in the field to provide the current status and future perspectives on the pathophysiology of headaches. We hope that this book will not only provide interesting reading but also serve as a useful reference in the field of headache research. Copenhagen, Denmark Florence, Italy Messoud Ashina Pierangelo Geppetti vii
Contents 1 Anatomy of Headache...................................... 1 Hayrunnisa Bolay, Karl Messlinger, Mária Dux, and Didem Akcali 2 Animal Models of Migraine................................. 31 Anna P. Andreou and Michael L. Oshinsky 3 Animal Models of Tension-Type Headache and Trigeminal Autonomic Cephalalgias...................... 67 Cristina Tassorelli, Rosaria Greco, and Simon Akerman 4 Genetics of Headache...................................... 83 Cherubino Di Lorenzo, Filippo M. Santorelli, and Arn M.J.M. van den Maagdenberg 5 Human Models of Primary Headaches........................ 101 Henrik Winther Schytz and Guus G. Schoonman 6 Imaging of Migraine....................................... 117 Michaela Andelova, David Borsook, and Till Sprenger 7 Imaging of Other Primary Headaches........................ 137 Sarah Miller and Manjit S. Matharu 8 Neurophysiology of Migraine................................ 155 Gianluca Coppola, Francesco Pierelli, Petter M. Omland, and Trond Sand 9 Neurophysiology of Other Primary Headaches................. 175 Anna Ambrosini and Gianluca Coppola 10 Biochemistry of Primary Headaches.......................... 185 Paola Sarchielli, Stefano Caproni, Cinzia Costa, Delia Szok, and Janos Tajti ix
x Contents 11 Pathophysiology of Migraine: Current Status and Future Directions...................................... 217 Jakob Møller Hansen and Dan Levy 12 Pathophysiology of TTH: Current Status and Future Directions...................................... 235 Sait Ashina and Lars Bendtsen 13 Pathophysiology of Cluster Headache: Current Status and Future Directions...................................... 247 Mark Obermann and Manjit Matharu 14 Pathophysiology of Medication Overuse Headache: Current Status and Future Directions........................ 259 Signe Bruun Munksgaard and Frank Porreca