engleski

EXPERIMENTAL MODELS OF MIGRAINE

Migraine is a very common neurological condition, clinically presented with debilitating headache, affecting over 10 percent of the population, . It can be accompanied with symptoms of vision distortion, aura. The main pathophysiological mark is neurogenic inflammation, presented as vasodilatations of dural vassals and extravasation of plasma proteins. Small experimental animals rat and mice do not suffer from migraine and there is a need for reliable experimental model to test existing and experimental drugs and to better understand pathophysiology of migraine. Trigeminovascular or neurovascular theory of migraine is a dominant hypothesis about migraine pathophysiology. Basically it connects pain with release of vasodilatatory neuropeptides (CGRP, supstance P) from peripheral sensory nerve endings innervating dural and cranial blood vessels. Accordingly the mechanism of action of most important antimigraine drugs i.e. ergots and triptans is to prevent release of vasadilatator neuropeptides from peripheral sensory nerve endings, and consequently prevent vasodilatation. Classical animal model of migraine is neurogenic, dural extravasation (sterile inflammation) induced by electrical stimulation of rat trigeminal ganglion. This model, mostly used in decerebrated animals, was used to determine the preclinical pharmacological effectiveness of all known antimigraine drugs (ergotamine, sumatriptan, act.). This model, together with research on isolated trigeminal ganglia contributed significantly to creation of trigemino-vascular theory of migraine. Some recent neuroimaging studies in humans apparently confirmed the existence of dural vasodilatation in the course of migraine. However in mentioned animal models vasodilatation and extravasation were studied separately from pain as a second hallmark of migraine. Important model of experimentally induced headache in trigeminal region is model of infraorbital nerve constriction injury (IoNC), which leads to development of trigeminal neuropathy, which can be measured as mechanical allodynia. This model was also used to examine effects of drugs used in migraine, like sumatriptan. In several case reports and in one controlled study it was show that that peripheral nerve injury can be cause of migraine in some patient. We used IoNC to investigate for the first time, whether peripheral nerve injury itself can elicit neurogenic dural extravasations. If so this model would be useful to investigate new antimigraine drugs and it would be possible to measure both mechanical allodynia and dural extravasations, core features of migraine. Experiments are in progress. Neuropathic pain assessed by measurement of mechanical allodynia (by von Frey filaments) was accompanied by bilateral dural extravasations of Evans blue - plasma protein complexes. Details will be presented. Acknowledgement: The experiments were approved by the Ethical Committee of the University of Zagreb, School of Medicine (permit No. 07-76/2005-43). This research was supported by Croatian Ministry of Science, Education and Sport and Deutscher Academischer Austauch Dienst (DAAD).

migrena; ekstravazacija; trigeminalni sustav; neurogena upala

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