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Headache
Emerging Treatments in Headache
a report by
Christina Sun-Edelstein, MD
1
and Alan M Rapoport, MD
2
1. Headache Neurologist, The New York Headache Center; 2. Clinical Professor of Neurology, The David Geffen School of Medicine,
University of California, Los Angeles, and Founder and Director Emeritus, New England Center for Headache
Migraine is a common and disabling disease, with a one-year of cortical neurons that gradually spreads across the cortex. This wave
prevalence of 12% in Western countries such as the US.
1
It is associated of depolarization occurs in conjunction with a wave of oligemia.
6–10
with significant societal costs in terms of pain, bedridden days, and lost Activation of the N-methyl-D-aspartate (NMDA) receptor subtype
days of work. Although the development and availability of triptans is required to trigger CSD in the rat cerebral cortex
11
and in human
over the past 17 years has revolutionized the acute treatment of neocortical tissues.
12
A similar phenomenon is hypothesized to
migraine, many patients report an incomplete or delayed response, occur spontaneously in humans, producing the aura. Recent evidence
while others experience intolerable adverse events.
2,3
Furthermore, obtained from functional magnetic resonance imaging,
13
epidural
triptans are contraindicated in patients with cardiovascular disease electrophysiological recordings,
14–16
and intracortical multiparametric
because of their vasoconstrictive activity. Therefore, other options are electrodes
17
have supported this hypothesis. The mechanism by
needed for those who do not respond optimally to triptans, as well as which the headache phase develops from the aura is unknown
for those with possible drug–drug interactions, contraindications, or and somewhat controversial, but it may be related to the cortical
risk factors. Additional goals for medications in development include release of CGRP, nitric oxide, arachidonic acid, or various ions and their
rapid onset of action, bypassing the gastrointestinal (GI) tract, sustained effects via the trigeminal nerve into the brainstem and back to the
treatment response, and solid safety and tolerability profiles. In this dural blood vessels.
18,19
overview of emerging treatments in headache, the current
understanding of migraine pathophysiology will be outlined and The rationale of the emerging therapies is based on the understanding
medical and surgical therapies at various stages of development will be of the above pathophysiology, with various treatments targeting
discussed. Advances in headache diagnosis and classification will also different components of the operative pathways discussed above.
be discussed in detail.
Migraine Pathophysiology
Christina Sun-Edelstein, MD, is a Headache Neurologist at
the New York Headache Center. She is a board-certified
In recent years, significant advances have been made in the
neurologist with subspecialty training and experience in
understanding of migraine pathophysiology. Although the exact
both headache and epilepsy. Dr Sun-Edelstein’s awards
etiology remains to be defined, the currently prevailing theories are
and honors include the American Academy of Neurology's
Resident Scholarship Award, the David Coddon Memorial
based on a hyperexcitable ‘trigeminovascular complex,’ and possibly
Award, the American Headache Society’s Clinical
cortex, in patients who are genetically predisposed to migraine. In
Fellowship Award, and the American Headache Society’s
these susceptible individuals, the trigeminovascular neurons release
Travel Award. She has also been published in academic
journals such as Archives of Neurology and Headache. After graduating from the State
neurotransmitters, such as calcitonin gene-related peptide (CGRP) and
University of New York Brooklyn College of Medicine with honors, she completed her
substance P, when headache triggers are encountered. This leads to
neurology residency at Mount Sinai Medical Center in New York. She subsequently spent a
vasodilation, mast cell degranulation, increased vascular permeability,
year in Melbourne, Australia as an Epilepsy Fellow at St Vincent’s Hospital, and then
returned to New York for her fellowship training in Headache Medicine at Roosevelt
and blood vessel edema, resulting in meningeal neurogenic
Hospital’s Headache Institute.
inflammation. This nociceptive information is transmitted from the
christinaksun@yahoo.com
periphery along the trigeminal nerve to the brainstem trigeminal
nucleus caudalis, and then to the thalamic nuclei and the cortex, Alan M Rapoport, MD, is a Clinical Professor of Neurology at The David Geffen School
where migraine pain is ultimately perceived.
4
The locus coeruleus,
of Medicine at the University of California, Los Angeles, and a founder and Director
Emeritus of the New England Center for Headache. He is board-certified in neurology and
which contains noradrenergic neurons, the dorsal raphe nuclei, which
headache medicine, and has co-authored more then 200 articles, chapters, and posters on
consist of serotoninergic neurons, and the periaqueductal gray also headache. He is an Editor of Headache, CNS Drugs, and Neurology Reviews. Dr Rapoport has
play modulatory roles in the transmission of pain.
5 served on the Board of Directors of the American Headache Society (AHS), formerly the
American Association for the Study of Headache (AASH), and is Past President of the
Fairfield County Neurological Society, the Founding President of the Headache Cooperative
The aura of migraine can be explained by the phenomenon of ‘cortical of New England (HCNE), the founding Director of the Headache Cooperative of the Pacific
spreading depression’ (CSD). In experimental animals and in human
and the Chairman of the Education and Membership Sub-Committee of the International
Headache Society (IHS).
neocortical and hippocampal tissue in vitro, CSD occurs when
an electric or chemical stimulus is applied to the cerebral cortex,
alanrapoport@gmail.com
resulting in an excitation followed by a prolonged depolarization
© TOUCH BRIEFINGS 2008
21
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