Brainstem pain-modulating systems in migraine-related photophobia

描述（由申请人提供）：偏头痛是最常见的神经系统疾病，在任何一年都会影响超过10%的人口，其中超过一半的人报告严重损害。对许多患者来说，偏头痛发作的一个严重，甚至致残的组成部分是恐惧症，但神经科学家刚刚开始调查潜在的 神经生物学机制本申请测试了已经涉及偏头痛相关疼痛的脑干疼痛调节回路也有助于偏头痛相关恐惧症的总体假设。这一假说是基于完全出乎意料的观察，即在偏头痛的动物模型中，延髓头端腹内侧的疼痛调节神经元（一个重要的脑干疼痛调节系统的最终输出）产生光反应，尽管它们在正常条件下对光没有反应。在使用硝酸甘油偏头痛大鼠模型的三个特定目标中，我们将记录已识别的疼痛调节神经元中的光诱发活动，并确定这是否是偏头痛特有的。我们还将确定疼痛调节系统是否有助于光厌恶和光诱导的疼痛增强。最后，我们将找出光进入痛觉调节系统的可能途径.目前的建议汇集了电生理学和行为学的方法，以显示光如何参与疼痛调节系统，以产生恐惧症。这些研究将为偏头痛相关的神经生物学机制提供见解，这是开发新的偏头痛治疗方法的关键基础信息。

DESCRIPTION (provided by applicant): Migraine is the most common neurological disorder, and affects over 10% of the population in any given year, with over half of these individuals reporting severe impairment. For many patients, a severe, even disabling, component of the migraine attack is photophobia, yet neuroscientists are just starting to investigate the underlying neurobiological mechanisms. The present application tests the overarching hypothesis that brainstem pain-modulating circuits, already implicated in migraine-related pain, also contribute to migraine-related photophobia. This hypothesis is based on the entirely unexpected observation that pain-modulating neurons in the rostral ventromedial medulla, the final output of an important brainstem pain-modulating system, develop photoresponsiveness in animal models of migraine headache, although they do not respond to light under normal conditions. In three Specific Aims using the nitroglycerin migraine model in the rat, we will document light-evoked activity in identified pain-modulating neurons and determine whether this is specific to migraine. We will also determine whether pain- modulating systems contribute to light aversion and light-induced pain enhancement. Finally, we will identify possible pathways through which light gains access to pain- modulating systems. The present proposal brings together electrophysiological and behavioral approaches to show how light engages pain-modulating systems to produce photophobia. These studies will provide insights into the neurobiological mechanisms of migraine-related photophobia, fundamental information critical for developing new migraine treatments.