Erdener S E, Dalkara T
Department of Neurology, Faculty of Medicine, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Br J Pharmacol. 2014 Oct;171(20):4575-94. doi: 10.1111/bph.12651. Epub 2014 Jul 1.
Similarities between laboratory animals and humans in anatomy and physiology of the cephalic nociceptive pathways have allowed scientists to create successful models that have significantly contributed to our understanding of headache. They have also been instrumental in the development of novel anti-migraine drugs different from classical pain killers. Nevertheless, modelling the mechanisms underlying primary headache disorders like migraine has been challenging due to limitations in testing the postulated hypotheses in humans. Recent developments in imaging techniques have begun to fill this translational gap. The unambiguous demonstration of cortical spreading depolarization (CSD) during migraine aura in patients has reawakened interest in studying CSD in animals as a noxious brain event that can activate the trigeminovascular system. CSD-based models, including transgenics and optogenetics, may more realistically simulate pain generation in migraine, which is thought to originate within the brain. The realization that behavioural correlates of headache and migrainous symptoms like photophobia can be assessed quantitatively in laboratory animals, has created an opportunity to directly study the headache in intact animals without the confounding effects of anaesthetics. Headache and migraine-like episodes induced by administration of glyceryltrinitrate and CGRP to humans and parallel behavioural and biological changes observed in rodents create interesting possibilities for translational research. Not unexpectedly, species differences and model-specific observations have also led to controversies as well as disappointments in clinical trials, which, in return, has helped us improve the models and advance our understanding of headache. Here, we review commonly used headache and migraine models with an emphasis on recent developments.
实验动物与人类在头部伤害感受通路的解剖学和生理学方面的相似性，使科学家能够创建成功的模型，这些模型为我们理解头痛做出了重大贡献。它们在新型抗偏头痛药物的研发中也发挥了重要作用，这些药物不同于传统的止痛药。然而，由于在人体中测试假设的机制存在局限性，对偏头痛等原发性头痛疾病的潜在机制进行建模一直具有挑战性。成像技术的最新进展已开始填补这一转化差距。患者偏头痛先兆期间皮质扩散性去极化（CSD）的明确证明，重新唤起了人们对在动物中研究CSD的兴趣，将其作为一种可激活三叉神经血管系统的有害脑事件。基于CSD的模型，包括转基因模型和光遗传学模型，可能更真实地模拟偏头痛中的疼痛产生，偏头痛被认为起源于大脑内部。认识到可以在实验动物中定量评估头痛和畏光等偏头痛症状的行为相关性，为直接研究完整动物的头痛创造了机会，而不会受到麻醉剂的混杂影响。给人类施用硝酸甘油和降钙素基因相关肽（CGRP）诱导的头痛和偏头痛样发作，以及在啮齿动物中观察到的平行行为和生物学变化，为转化研究创造了有趣的可能性。不出所料，物种差异和特定模型的观察结果也导致了临床试验中的争议和失望，而这反过来又帮助我们改进模型并加深对头痛的理解。在此我们综述常用的头痛和偏头痛模型，并重点介绍最新进展。
