Brainstem pain-modulating systems in migraine-related photophobia

描述(申请人提供)：偏头痛是最常见的神经疾病，任何一年都会影响超过10%的人口，其中超过一半的人报告说严重受损。对于许多患者来说，偏头痛发作的一个严重的、甚至是致残的组成部分是畏光，然而神经科学家们才刚刚开始研究其潜在的原因 神经生物学机制。目前的应用测试了最重要的假设，即已经与偏头痛相关的疼痛有关的脑干疼痛调制回路也有助于偏头痛相关的畏光。这一假说是基于完全出人意料的观察结果，即在偏头痛的动物模型中，头端延髓腹内侧部的疼痛调制神经元--一个重要的脑干疼痛调制系统的最终输出--会发展出光反应，尽管它们在正常情况下对光没有反应。在使用硝酸甘油偏头痛模型的三个特定目标中，我们将记录已识别的疼痛调制神经元中的光诱发活动，并确定这是否为偏头痛所特有。我们还将确定疼痛调制系统是否有助于光厌恶和光诱导的疼痛增强。最后，我们将确定光进入痛觉调节系统的可能途径。目前的提议结合了电生理和行为方法来展示光是如何参与疼痛调制系统来产生恐光的。这些研究将为偏头痛相关畏光的神经生物学机制提供洞察力，这是开发新的偏头痛治疗方法的关键基础信息。 公共卫生相关性：偏头痛仍然是导致残疾的最常见的神经原因，目前的治疗方案对许多患者无效。偏头痛患者通常避免光线，因为光线会增加他们的头痛疼痛。这项申请中提出的工作旨在了解大脑自身的疼痛调制系统在偏头痛期间的光敏性中所起的作用，这最终将有助于我们开发更好的偏头痛治疗方法。

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. PUBLIC HEALTH RELEVANCE: Migraine remains the most common neurological cause of disability, and current treatment options are ineffective for many patients. Migraine patients often avoid light, because light increases their headache pain. The work proposed in this application seeks to understand the role of the brain's own pain-modulating systems in photosensitivity during migraine, which should ultimately help us develop better treatments for migraine pain.