Role of CGRP in the association between migraine and obesity

CGRP 在偏头痛和肥胖之间的关系中的作用

• 批准号: 7708685
• 负责人: Ana Recober-Montilla
• 金额: $ 17.35万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-03 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7708685
• 关键词: Address; Animal Model; Behavioral; Biological; Biological Assay; Biology; Brain; Calcitonin; Calcitonin Gene-Related Peptide; Calcitonin-Gene Related Peptide Receptor; Chemicals; Chronic; Development; Diet; Disease; Dura Mater; Exhibits; Face; Facial Pain; Frequencies; Functional disorder; Future; General Population; Genes; Goals; Grant; Headache; Headache Disorders; Human; Individual; Iowa; K-Series Research Career Programs; Knowledge; Lead; Ligands; Link; Low Prevalence; Measurable; Measures; Mediating; Mentored Clinical Scientist Development Award (K08); Mentors; Mentorship; Messenger RNA; Migraine; Mission; Molecular; Molecular Biology Techniques; Mus; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neuromodulator; Neurons; Nociception; Obesity; Pain; Pain Research; Pathway interactions; Patient Care; Peptide Synthesis; Phenotype; Photophobia; Physicians; Plasma; Play; Prevalence; Preventive; Principal Investigator; Production; Proteins; Public Health; Publishing; Reporting; Risk Factors; Rodent; Role; Scientist; Societies; Structure of trigeminal ganglion; Testing; Therapeutic; Training; Transgenic Mice; Trigeminal Nuclei; Trigeminal System; United States National Institutes of Health; Universities; allodynia; base; career; cost; mouse model; nervous system disorder; neuronal excitability; overexpression; pain behavior; prevent; public health relevance; receptor; receptor-activity-modifying protein; response; therapeutic target; tool; translational study

DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Development Award (K08) will allow me to build a career as a successful independent physician-scientist devoted to the study of migraine and other headache disorders. Drs. Russo and Hammond will be my mentors at The University of Iowa. My long-term career goal is to identify therapeutic targets to prevent the development of chronic migraine based on biological information gained from the study of animal models. My immediate goal is to identify the mechanisms of interaction between obesity and migraine that lead to the development of chronic migraine. The objective of this proposal is to test the concept that calcitonin gene-related peptide (CGRP) represents a biological link between obesity and migraine. CGRP plays an important role in migraine and possibly in obesity. Our central hypothesis is that obesity in mice increases CGRP production and activity in trigeminal pathways, which leads to enhanced pain and other phenotypic correlates of migraine. A set of 3 complementary, but independent, specific aims are proposed. In Aim 1 we will use behavioral and immunohistochemical studies to establish the influence of obesity in the trigeminal nociceptive pathway, which is central in migraine pathophysiology. In Aim 2 we will employ molecular biology techniques to determine the effect of obesity on CGRP levels and receptor activity. In Aim 3 we will use a behavioral and pharmacological approach to assess whether obesity enhances migraine-like features of a transgenic mouse model of migraine. The results of these translational studies will provide fundamental knowledge necessary for future human studies. A better understanding of the interaction between obesity and migraine will have a significant impact in patient care. The objective of this proposal is highly relevant to the mission of the NINDS as it seeks to reduce the burden of migraine, a neurological disease with a prevalence of 12% in the general population worldwide. The identification of factors that contribute to the development of chronic migraine, and their mechanisms of action, will allow a preventive therapeutic approach. This will eventually lead to a lower prevalence of chronic migraine and a have a positive impact in our society. Public Health Relevance: Migraine is a common, disabling disorder that is aggravated by obesity. Both conditions represent serious public health problems worldwide, with a high cost to society. Understanding the way obesity and migraine interact is important to develop especific treatments to prevent the progression to chronic migraine. These studies will be the first to address the molecular basis of the association between obesity and migraine.

描述（由申请人提供）：这一指导的临床科学家发展奖（K08）将使我能够成为成功的独立医师科学家，致力于研究偏头痛和其他头痛障碍。博士。鲁索（Russo）和哈蒙德（Hammond）将成为爱荷华大学的导师。我的长期职业目标是确定基于动物模型研究所获得的生物学信息，以防止慢性偏头痛的发展。我的直接目标是确定肥胖与偏头痛之间的相互作用机制，从而导致慢性偏头痛的发展。该建议的目的是测试降钙素基因相关肽（CGRP）代表肥胖与偏头痛之间的生物学联系的概念。 CGRP在偏头痛和肥胖症中起着重要作用。我们的中心假设是，小鼠的肥胖症增加了三叉神经途径的CGRP产生和活性，从而导致疼痛增强和偏头痛的其他表型相关性。提出了一组3个互补但独立的特定目标。在AIM 1中，我们将使用行为和免疫组织化学研究来确定肥胖症在三叉神经伤害途径中的影响，这在偏头痛病理生理学中是核心。在AIM 2中，我们将采用分子生物学技术来确定肥胖对CGRP水平和受体活性的影响。在AIM 3中，我们将使用一种行为和药理方法来评估肥胖是否增强了偏头痛的转基因小鼠模型的偏头痛特征。这些翻译研究的结果将为未来的人类研究提供必要的基本知识。更好地了解肥胖与偏头痛之间的相互作用将对患者护理产生重大影响。 该提案的目的与Ninds的使命高度相关，因为它试图减轻偏头痛的负担，这是一种神经系统疾病的负担，在全球一般人群中占12％。鉴定有助于发展慢性偏头痛及其作用机理的因素将允许一种预防性治疗方法。这最终将导致慢性偏头痛的患病率较低，并对我们的社会产生积极影响。 公共卫生相关性：偏头痛是一种常见的残疾疾病，肥胖症加剧。两种情况都代表了全球严重的公共卫生问题，对社会的成本很高。了解肥胖和偏头痛相互作用对于开发特定治疗以防止慢性偏头痛的发展很重要。这些研究将是第一个解决肥胖与偏头痛之间关联的分子基础的研究。