Experimental Migraine Models and Their Relevance in Migraine Therapy

Abstract

Although the understanding of migraine pathophysiology is incomplete, it is now well accepted that this neurovascular syndrome is mainly due to a cranial vasodilation with activation of the trigeminal system. Several experimental migraine models, based on vascular and neuronal involvement, have been developed. Obviously, the migraine models do not entail all facets of this clinically heterogeneous disorder, but their contribution at several levels (molecular, in vitro, in vivo) has been crucial in the development of novel antimigraine drugs and in the understanding of migraine pathophysiology. One important vascular in vivo model, based on an assumption that migraine headache involves cranial vasodilation, determines porcine arteriovenous anastomotic blood flow. Other models utilize electrical stimulation of the trigeminal ganglion/nerve to study neurogenic dural inflammation, while the superior sagittal sinus stimulation model takes into account the transmission of trigeminal nociceptive input in the brainstem. More recently, the introduction of integrated models, namely electrical stimulation of the trigeminal ganglion or systemic administration of capsaicin, allows studying the activation of the trigeminal system and its effect on the cranial vasculature. Studies using in vitro models have contributed enormously during the preclinical stage to characterizing the receptors in cranial blood vessels and to studying the effects of several putative antimigraine agents. The aforementioned migraine models have advantages as well as some limitations. The present review is devoted to discussing various migraine models and their relevance to antimigraine therapy.

Current and prospective pharmacological targets in relation to antimigraine action

“…Several migraine models, based on vascular and neuronal involvement, show that different receptors could be targeted for the development of antimigraine compounds (Arulmani et al 2006;De Vries et al 1999b). In this context, it should be emphasized that the currently available migraine models do not entail all facets of this clinically heterogeneous disorder but are rather based on some of the symptoms observed in migraine (e.g., focus on only neuronal or vascular aspects).…”

“…CTZ: Chemoreceptor trigger zone. Redrawn from Saxena and Tfelt-Hansen (2006) trigeminal ganglion or systemic administration of capsaicin, has allowed studies on the activation of the trigeminal system and its effects on the cranial vasculature (for review, see Arulmani et al 2006). This review also contains data on the ability of several drugs to inhibit plasma protein extravasation (e.g., Weiss et al 2006), although it should be kept in mind that extravasation inhibitors, such as CP-122,288 (Roon et al 2000), the neurokinin-1 receptor antagonist lanepitant (Goldstein et al 2001a;Goldstein et al 1997), and the mixed ET A /ET B receptor antagonist bosentan (May et al 1996) proved ineffective in the treatment of migraine.…”

Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries

“…In contrast, the physiology and pharmacology of migraine pain is undoubtedly associated with activation of the trigeminovascular sensory nervous system (Silberstein, 2004;Arulmani et al, 2006). The trigeminovascular system contains calcitonin gene-related peptide (CGRP)-positive trigeminal sensory nerves that innervate cerebral and meningeal blood vessels and with their central synapses mediate pain signal transmission to central second-order sensory neurons within the brainstem trigeminal nucleus caudalis.…”

Magnetic resonance spectroscopy in migraine: What have we learned so far?

“…Experimental migraine models have been useful but incomplete in reflecting the full scope of the human condition (2). At present, no integrative model exists to explain this multifaceted syndrome.…”