Migraine and Headache Pathophysiology
Lars Edvinsson, ed.
Martin Dunitz, 1999, 175 pages

migraine is a recurring, prolonged, and often debilitating type of headache that produces, in addition to head pain and nausea, characteristic neurological phenomena such as visual disturbances and photophobia as well as systemic disturbances such as water retention and intestinal disturbances. Recent research has led to the discovery of 5-hydroxytryptamine (5HT-1B/1D) receptor agonists such as zolmitriptan and sumatriptan that can acutely mitigate the symptoms more effectively than the earlier anti-serotonergic alkaloids ergotamine and dihydroergotamine. However, the triptans cannot prevent migraines and have side effects that can range from nasal decongestion to, in some cases, severe non-migraine rebound headache. Hence migraines are a topic of intense research.

This book is not a textbook, but a collection of short biomedical reviews on the subject. The emphasis is on mainstream studies of the physiology of intracranial blood vessels and the neurotransmitters that affect them and their receptor pharmacology. There is some information on the medicinal chemistry of anti-migraine drugs, and much healthy speculation, but no information on symptomology, extra-vascular effects, or unconventional approaches to treatment such as magnesium infusion or neurosteroids.

As described in several of the chapters, the mechanism of pain generation in migraine involves release of vasoactive peptides such as substance P and calcitonin gene-related peptide (CGRP) from c-fibers in the trigeminal ganglion. These peptides act as potent vasodilators, and are part of the trigeminovascular reflex whose function is to counteract vasospasm. Their effects are counterbalanced by 5HT, which causes vasoconstriction and inhibits neurogenic CGRP release. Research on 5HT receptors suggests that these functions may be mediated by different receptor subtypes. Hargreaves et al. point out, however, that the vasodilatation theory does not explain the inability of vasoconstrictors like epinephrine to cure migraine. Other signaling molecules such as neurokinin A, a pro-inflammatory peptide found in the trigeminal ganglion, and nitric oxide, a widespread endogenous vasodilator, have been suggested to play a role in migraine. Some research has therefore shifted to anti-inflammatory agents and nitric oxide synthase inhibitors. This has produced some promising candidates. However, little progress has been made in understanding the basic causes of migraines. Amazingly, as G.R. Martin et al. point out, even the precise site of action of aspirin and similar non-steroidal anti-inflammatory drugs is still not known with certainty.

An alternative theory of the pathogenesis of migraine is the theory of cortical spreading depression, which postulates that extracellular ionic imbalances, rather than primary vascular effects, are responsible for migrainogenesis. This theory and its limitations are well described in the chapters by Read et al. and L. Friberg.

Advanced Therapy of Headache, 2nd ed.
Purdy, Rapoport, Sheftell, and Tepper, eds.
BC Decker, 2005 (339 pages + CD)

hy read a book about other people having headaches? For the same reason people watch other people playing football or having sex instead of just doing it themselves: you may learn some useful pointers, and there is less risk of injuring yourself. Each of the 58 chapters in this book starts with a real clinical case, followed by the correct diagnosis and a brief discussion. The clinical cases presented here are not particularly tough to diagnose if you have any neurology background, but they'd be invaluable in the clinic, where information from patients is often incorrect or misleading. Patients could also benefit from reading this book: as one author says, patients frequently misdiagnose their own headaches and often neglect to mention critical symptoms. And reading some of the more severe cases might give them a little perspective: their headache could have been much, much worse.

may 29, 2011