Animal models of migraine: looking at the component parts of a complex disorder

Abstract

Animal models of human disease have been extremely helpful both in advancing the understanding of brain disorders and in developing new therapeutic approaches. Models for studying headache mechanisms, particularly those directed at migraine, have been developed and exploited efficiently in the last decade, leading to better understanding of the potential mechanisms of the disorder and of the action for antimigraine treatments. Model systems employed have focused on the pain-producing cranial structures, the large vessels and dura mater, in order to provide reproducible physiological measures that could be subject to pharmacological exploration. A wide range of methods using both in vivo and in vitro approaches are now employed; these range from manipulation of the mouse genome in order to produce animals with human disease-producing mutations, through sensitive immunohistochemical methods to vascular, neurovascular and electrophysiological studies. No one model system in experimental animals can explain all the features of migraine; however, the systems available have begun to offer ways to dissect migraine's component parts to allow a better understanding of the problem and the development of new treatment strategies.

Preliminary Studies on the Antinociceptive Activity of Vaccinium ashei Berry in Experimental Animal Models

“…The use of different models is significant in the detection of antinociceptive properties in a substance, considering that using a variety of stimuli can recognize different types of pain and reveal the actual nature of antinociceptive test drugs. 21 The acetic acid-induced writhing test is very sensitive and capable of detecting antinociceptive effects of substances at dose levels that may appear inactive in other methods, such as the hot plate test. 22 The abdominal constrictions provoked by acetic acid in the intraperitoneal cavity triggers a diversity of mediators, such as bradykinin and prostaglandins (prostaglandin I 2 ), as well as some cytokines such as interleukin1b, tumor necrosis factor-a, and interleukin-8.…”

Vascular Actions of Estrogens: Functional Implications

“…If the genetic variant results in decreased activity of eNOS, these results are difficult to interpret within the context that increased production of NO may trigger migraine (Thomsen and Olesen, 2001). Some evidence implicates neuronally derived NO in the etiology of migraine, but no association of migraine with genetic variation of neuronal nitric oxide synthase was found (Johnson et al, 2005;Bergerot et al, 2006;Borroni et al, 2006). More information is needed regarding estrogenic modulation of all three isoforms of nitric oxide synthase in the cerebrovascular unit.…”

“…As discussed above (section V.C), estrogen receptors are located within brain nuclei that innervate the cerebral vasculature as well as other nuclei regulating cardiovascular function (Martin and Behbehani, 2006). Thus, in addition to influencing adrenergic mechanisms, estrogen may also modulate central opioidergic tone, release of peptidergic transmitters from trigeminal nuclei, and the GABAergic system, perhaps modulating NO (Johnson et al, 2005;Bergerot et al, 2006;Brandes, 2006;Martin and Behbehani, 2006;Puri et al, 2006). Because ER␣ stimulates NO production in vascular endothelium, there might also be direct modification of migraine occurrence through this pathway.…”

Neurons of the Dopaminergic/Calcitonin Gene-Related Peptide A11 Cell Group Modulate Neuronal Firing in the Trigeminocervical Complex: An Electrophysiological and Immunohistochemical Study

“…We used a durovascular model that has been highly predictive of translational outcomes in migraine (Bergerot et al, 2006) to test this question. Additionally, because CGRP has been reported in both the A11 and the neighboring subparafascicular nucleus (Spf) (Yasui et al, 1989(Yasui et al, , 1991Orazzo et al, 1993), and the literature is inconsistent about whether the Spf is part of the A11 nucleus (Takada et al, 1988), we used immunohistochemistry to characterize the area.…”