Migraine is a chronic and disabling disorder of the brain that affects up to 15% of the population worldwide. A great unmet need exists for novel effective, safe, and well-tolerated pharmacotherapies of migraine. Animal models are indispensable tools for the development of new therapy for migraine management. Creative Biolabs has established several rodent migraine models and conducts contract studies to evaluate the efficacy of novel therapeutic agents. Study designs and protocols are flexible and can be adapted according to clients' needs.
Introduction of Migraine
Migraine is defined as a multifactorial and episodic disorder which is featured with unilateral, hemicranial, throbbing headache that often accompanied by nausea and vomiting and aggravated by movement, sound, and light. Migraine has two major clinical subtypes: migraine with and without aura. One-third of the patients with migraine experience aura, that is, transient focal neurological symptoms like sensory or motor deficits.
Yet not fully understand, the pathophysiology of migraine is thought to involve the activation of the trigeminal afferents, which densely innervate dural structures and send projections to second-order neurons of trigeminal nucleus caudalis and the C1-C2 region of the spinal cord (trigeminocervical complex). The trigeminovascular system includes the pseudounipolar trigeminal ganglion that projects into the trigeminal nucleus caudalis in the medullary spinal cord and has a peripheral projection from the ophthalmic division of the trigeminal ganglion, which innervates the cranial blood vessels and pain-sensitive dura mater. Numerous potent vasodilator peptides such as the calcitonin gene-related peptide (CGRP) are presented in the trigeminal ganglion and project nerve fibers to cranial vessels. Several lines of evidence suggest that cortical spreading depression (CSD) causes aura symptoms and impacts both short-term and long-term neurovascular function. It has also been documented that migraine pain in humans arises due to the stimulation of blood vessels in dura mater. These points raise the concept of involvement of cerebrovascular system of dura mater in the pathophysiology of migraine.
Fig.1 Major structures and pathways relevant to current animal models of headache: migraine pathophysiology involves activation, or the perception of activation, of trigeminal sensory afferents of the ophthalmic division of the trigeminal nerve that innervate both dural and facial structures. (Andreou et al. 2010)
Animal models of migraine have facilitated our understanding of migraine mechanisms and led the discoveries of specific migraine treatments, such as triptans and CGRP receptor inhibitors. However, no animal model that replicates all components of migraine currently exists due to the complexity of this disease. Creative Biolabs utilizes the most commonly used models of migraine to provide our clients with antimigraine drug development services:
Nitroglycerin (NTG)-Induced Model of Migraine
NGT infusion is the most widely used and trustworthy method to provoke migraine-like headaches in humans as well as in animals. The infusion of the nitric oxide donor NTG results in upregulation of proinflammatory mediators, macrophage activation, edema formation, and mast cell degranulation by its direct action on meningeal tissues and produces plasma protein extravasations (PPE). One of the most important advantages of the NGT-triggered headache model is the temporal control of events following NGT administration.
Cortical Spreading Depression (CSD) Model of Migraine Aura
Cortical spreading depression (CSD), which is known as a shift in cortical steady potential, results in an increase in the extracellular ions (K+), intracellular ions (Na+ and Ca2+), and neurotransmitter (glutamate). Studies have reported that CSD models are useful tools for testing current and novel prophylactic drugs, providing knowledge on mechanisms of action relevant for migraine.
The neurological platform of Creative Biolabs provides an extensive range of rodent neurological disease models. If you are interested, click the following links for more detailed description of each model:
Based on a group of scientists with proven in-depth expertise in pharmacology and efficacy studies and a set of behavioral and analytical methods at hand, Creative Biolabs is capable of offering comprehensive and individually tailored services with the best quality and the most reasonable prices for every specific project. We are happy to share our professional expertise with our clients to facilitate their brilliant studies. Contact us to start the conversation now.
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