Experimental animal models of migraine

Animal models of migraine have been widely used during the last decades to provide clues for understanding mechanisms underlying pathophysiology of migraine attacks and for developing specific therapeutic agents. They can be grouped into two main types: vascular and neurovascular. Trigemino-vascular system (TVS) is the most relevant efferent component and the mediators of its activity have been thoroughly studied along with some of the receptors involved to characterize anatomical and functional aspects of the system and to test efficacy and mechanisms of therapeutic agents. Neurovascular models are numerous. Plasma protein extravasation (PPE) model consists of measuring the amount of proteins leaking from vessels when TVS is either electrically or chemically stimulated and evaluating its blockade by systemically administered therapeutic agents of which specific receptors have also been identified. Activation of trigeminal nucleus caudalis (TNC) through meningeal stimulation of the superior sagittal sinus served to better understand the mechanisms of central nociceptive pathway. The cortical spreading depression (CSD) model has been used to activate the TVS through application of potassium chloride and evaluate Fos expression in the trigeminal nucleus caudalis (TNC). Finally, neurochemical, cerebrovascular, and nociceptive response to systemic or central administration of nitric oxide (NO) donors served to study central nociceptive pathway and autonomic response interaction. Transgenic mouse expressing human migraine mutations has been genetically engineered to provide an understanding of familial hemiplegic migraine (FHM). Animal models of migraine also served to better understand the role of hormones, genes, and environmental factors on migraine pathophysiology.