Mechanisms of pain modulation by the migraine drug sumatriptan

偏头痛药物舒马曲坦的疼痛调节机制

• 批准号: 8287548
• 负责人: ANDREW H AHN
• 金额: $ 18.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287548
• 关键词: Affect; Affective; Afferent Neurons; American; Amygdaloid structure; Analgesics; Animals; Area; Attention; Behavior; Behavioral; Biological Assay; Brain; Calcitonin Gene-Related Peptide; Cell Nucleus; Clinical; Comorbidity; Conflict (Psychology); Disease; Emotional; Foundations; Functional disorder; Funding; Future; Goals; Headache; Independent Scientist Award; Inflammation; K-Series Research Career Programs; Knowledge; Lateral; Lead; Medical; Migraine; Modality; Modeling; Molecular; Motivation; Neurobiology; Neurogenic Inflammation; Neurologic; Neurons; Neurosciences Research; Nociception; Outcome; Pain; Pain Measurement; Peer Review; Pharmaceutical Preparations; Phosphorylation; Phosphotransferases; Physicians; Positioning Attribute; Process; Productivity; Research Personnel; Rewards; Role; Scientist; Sensory; Simulate; Site; Source; Spinal; Spreading Cortical Depression; Stimulus; Sumatriptan; Symptoms; Techniques; Testing; Trigeminal Nuclei; United States; Withdrawal; Work; base; career; career development; design; disability; effective therapy; experience; extracellular; innovation; insight; nervous system disorder; neurochemistry; pain behavior; parabrachial nucleus; psychiatric disability; receptor; research and development; response; serotonin receptor; theories; therapeutic target

DESCRIPTION (provided by applicant): Migraine is a prevalent and disabling disorder that continues to confound best available medical therapy. An important obstacle to new more effective therapy is that we lack critical insights as to the relevant neurobiological targets. This is because the basic mechanisms contributing to this disorder remain elusive, and prevailing theories of the pathophysiology of migraine are based upon indirect or conflicting lines of evidence. Given what little direct evidence supports our understanding of migraine, any fundamental insight into the critical anti-migraine actions of sumatriptan action in the brain would be of great significance to our understanding of the disorder and the rational design of new therapies. The overall goal of this project is to elucidate the neurobiological actions of the migraine-specific drug sumatriptan. The inhibitory actions of sumatriptan in the periphery, on neurogenic inflammation and sensory neurons, are well described, but the mechanisms of sumatriptan in the brain remain virtually unexplored. This project focuses on the action of sumatriptan on pain-related circuits within the amygdala, and its influence on the affective-emotional processing of pain, through the activation of the 5HT1D receptor. Importantly, because a central clinical feature of migraine is the disturbance of the affective component of all sensory modalities, the modulation of the affective-emotional processing of pain by sumatriptan within the amygdala could potentially be a critical site for the anti-migraine activity of sumatriptan, and could be an important target for migraine therapy in the future. This applicant for a K02 Independent Scientist Career Development Award is a physician scientist with a longstanding commitment to a career in neuroscience research. This K02 award will support his continued career development and research that will lead to obtaining peer-reviewed, independent investigator-initiated funding.

描述（由申请人提供）：偏头痛是一种流行的致残性疾病，持续混淆现有的最佳药物治疗。新的更有效的治疗方法的一个重要障碍是，我们缺乏对相关神经生物学靶点的关键见解。这是因为导致这种疾病的基本机制仍然难以捉摸，并且偏头痛的病理生理学的流行理论是基于间接或相互矛盾的证据。鉴于几乎没有直接证据支持我们对偏头痛的理解，任何关于舒马曲坦在大脑中的关键抗偏头痛作用的基本见解对于我们理解这种疾病和合理设计新疗法都具有重要意义。 该项目的总体目标是阐明偏头痛特异性药物舒马曲坦的神经生物学作用。舒马曲坦在外周对神经源性炎症和感觉神经元的抑制作用已得到很好的描述，但舒马曲坦在脑中的作用机制实际上尚未探索。该项目的重点是舒马曲坦对杏仁核内疼痛相关回路的作用，以及通过激活5 HT 1D受体对疼痛的情感情绪处理的影响。重要的是，由于偏头痛的一个中心临床特征是所有感觉模态的情感成分的干扰，杏仁核内的舒马曲坦对疼痛的情感-情绪处理的调制可能是舒马曲坦抗偏头痛活性的关键部位，并且可能是未来偏头痛治疗的重要靶点。 K 02独立科学家职业发展奖的申请人是一位长期致力于神经科学研究的医生科学家。这个K 02奖将支持他继续职业发展和研究，这将导致获得同行评审，独立的赞助商发起的资金。