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2014 ; 171
(20
): 4575-94
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Modelling headache and migraine and its pharmacological manipulation
#MMPMID24611635
Erdener SE
; Dalkara T
Br J Pharmacol
2014[Oct]; 171
(20
): 4575-94
PMID24611635
show ga
Similarities between laboratory animals and humans in anatomy and physiology of
the cephalic nociceptive pathways have allowed scientists to create successful
models that have significantly contributed to our understanding of headache. They
have also been instrumental in the development of novel anti-migraine drugs
different from classical pain killers. Nevertheless, modelling the mechanisms
underlying primary headache disorders like migraine has been challenging due to
limitations in testing the postulated hypotheses in humans. Recent developments
in imaging techniques have begun to fill this translational gap. The unambiguous
demonstration of cortical spreading depolarization (CSD) during migraine aura in
patients has reawakened interest in studying CSD in animals as a noxious brain
event that can activate the trigeminovascular system. CSD-based models, including
transgenics and optogenetics, may more realistically simulate pain generation in
migraine, which is thought to originate within the brain. The realization that
behavioural correlates of headache and migrainous symptoms like photophobia can
be assessed quantitatively in laboratory animals, has created an opportunity to
directly study the headache in intact animals without the confounding effects of
anaesthetics. Headache and migraine-like episodes induced by administration of
glyceryltrinitrate and CGRP to humans and parallel behavioural and biological
changes observed in rodents create interesting possibilities for translational
research. Not unexpectedly, species differences and model-specific observations
have also led to controversies as well as disappointments in clinical trials,
which, in return, has helped us improve the models and advance our understanding
of headache. Here, we review commonly used headache and migraine models with an
emphasis on recent developments.
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