Stress: Potential Impact on an Animal Model of Endometriosis

压力：对子宫内膜异位症动物模型的潜在影响

• 批准号: 8180413
• 负责人: Caroline B Appleyard
• 金额: $ 42.42万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8180413
• 关键词: Absence of pain sensation; Adhesions; Adolescent; Adrenal Glands; Affect; Animal Model; Animals; Area; Behavior; Behavior Therapy; Behavioral; Binding; Blood Pressure; Brain; Brain region; Cells; Child; Chronic; Chronic Disease; Chronic stress; Clinical Management; Colon; Complex; Development; Diagnosis; Disease; Disease Progression; Dysmenorrhea; Dyspareunia; Endometrial; Environment; Equilibrium; Ethics; Etiology; Exhibits; Exposure to; Fertility; Fibrosis; Gastrointestinal Diseases; Genetic; Gland; Glucocorticoid Receptor; Goals; Growth; Health; Health Care Costs; Heart Rate; Hormonal; Human; Hydrocortisone; Hyperalgesia; Immune; Immune response; Immune system; Impairment; Infertility; Inflammation; Inflammation Mediators; Inflammatory; Interdisciplinary Study; Intervention; Intestines; Lesion; Life; Life Style; Ligaments; Link; Mammalian Oviducts; Mission; Modeling; Natural Killer Cells; Nerve; Nerve Growth Factors; Onset of illness; Operative Surgical Procedures; Opioid Receptor; Output; Ovarian Cysts; Ovary; Pain; Pain Clinics; Pain Disorder; Pathogenesis; Patients; Peripheral; Peritoneal; Personal Satisfaction; Phenotype; Physiological; Physiology; Prevalence; Probability; Process; Productivity; Rattus; Recurrence; Reporting; Research; Research Personnel; Rodent; Science; Severities; Severity of illness; Signs and Symptoms; Site; Stress; Students; Symptoms; Techniques; Testing; Tissue Sample; Training; Transplantation; Uncertainty; United States National Institutes of Health; Up-Regulation; Uterine cavity; Uterus; Vagina; Vesicle; Woman; Work; base; biological adaptation to stress; central pain; chronic pain; chronic pelvic pain; coping; cytokine; disease phenotype; endometriosis; experience; human disease; hypothalamic-pituitary-adrenal axis; immune function; mast cell; midbrain central gray substance; multidisciplinary; nerve supply; new therapeutic target; pain receptor; programs; psychologic; reproductive; stress management; stressor; theories; therapeutic target; translational study

DESCRIPTION (provided by applicant): Endometriosis is a chronic gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity, mainly in ovaries, fallopian tubes, cul-de-sac and the uterine ligaments. Theories of endometriosis suggest that its etiology arises from a complex interaction of both genetic and environmental influences. This condition is characterized by peritoneal inflammation, fibrosis, adhesions and ovarian cysts, which result in chronic pelvic pain, pain during intercourse (dyspareunia), painful periods (dysmenorrhea) and infertility. Still today, endometriosis remains a poorly understood condition that continues to incapacitate and affect the productivity and lifestyle of millions of women around the world. Research indicates that stress is a significant component of many recurrent and chronic health problems, including chronic pain disorders. The negative effects of stress on many diseases include impairment of immune function, increasing cortisol levels and alteration of the hormonal balance. It is generally accepted that dealing with the symptoms of endometriosis on a daily basis is stressful by itself. Circumstantial evidence suggests that a variety of stress management techniques, including effectively handling stressful situations and implementing lifestyle changes, can help women suffering from endometriosis and other reproductive disorders. However, whether stress affects the prevalence and progression of endometriosis in women is still unknown. This study will test the hypothesis that stress and its controllability, can affect disease progression and phenotype through different mechanisms, including dysregulation of the immune system and involvement of central pain centers, in an established animal model of endometriosis. The specific aims of this translational study will examine whether stress can exacerbate the development and progression of endometriosis, and determine whether the ability to control stress can decrease the extent of endometriosis. It will contribute to the goals of the AREA program by strengthening the institutional environment through support of an interdisciplinary group of experienced investigators with expertise in endometriosis, animal physiology and behavior. It will provide opportunities for exposure of students at various levels to multidisciplinary research areas, providing a unique training opportunity and further encouraging their continued studies in the biomedical sciences. The results of these studies are also expected to identify possible interventions that will ultimately help women affected by this disease to live healthy and productive lives, in accordance with the mission of the NIH. PUBLIC HEALTH RELEVANCE: Endometriosis is a poorly understood condition that incapacitates and affects the productivity and well- being of millions of women in their reproductive years around the world. These studies will contribute to our understanding of the impact of stress on the underlying pathophysiological mechanisms of endometriosis, and exacerbation of its painful symptoms, and to the possibility of implementing stress management interventions as a therapeutic target.

描述(申请人提供)：子宫内膜异位症是一种慢性妇科疾病，定义为子宫内膜腺和子宫内膜腔外的间质，主要位于卵巢、输卵管、死囊和子宫韧带。子宫内膜异位症的理论表明，其病因是由遗传和环境影响的复杂相互作用引起的。这种情况的特点是腹膜炎症、纤维化、粘连和卵巢囊肿，导致慢性盆腔疼痛、性交疼痛(性交困难)、痛经(痛经)和不孕不育。时至今日，子宫内膜异位症仍然是一种鲜为人知的疾病，它继续丧失能力，并影响世界各地数百万女性的生产力和生活方式。研究表明，压力是许多反复和慢性健康问题的重要组成部分，包括慢性疼痛障碍。压力对许多疾病的负面影响包括免疫功能受损、皮质醇水平升高和激素平衡改变。人们普遍认为，每天处理子宫内膜异位症的症状本身就有压力。间接证据表明，各种压力管理技术，包括有效地处理压力情况和改变生活方式，可以帮助患有子宫内膜异位症和其他生殖障碍的妇女。然而，应激是否影响女性子宫内膜异位症的患病率和进展尚不清楚。这项研究将在已建立的子宫内膜异位症动物模型中检验压力及其可控性可以通过不同的机制影响疾病进展和表型的假设，包括免疫系统的失调和中枢疼痛中心的参与。这项翻译研究的具体目的将考察压力是否会加剧子宫内膜异位症的发展和进展，并确定控制压力的能力是否可以降低子宫内膜异位症的程度。它将通过支持一个在子宫内膜异位症、动物生理学和行为方面具有专业知识的经验丰富的跨学科研究人员小组来加强机构环境，从而为区域计划的目标做出贡献。它将为不同水平的学生提供接触多学科研究领域的机会，提供一个独特的培训机会，并进一步鼓励他们在生物医学科学方面继续学习。根据美国国立卫生研究院的使命，这些研究的结果还有望确定可能的干预措施，最终帮助受这种疾病影响的妇女过上健康和富有成效的生活。 公共卫生相关性：子宫内膜异位症是一种知之甚少的疾病，它使世界各地数百万育龄妇女的生产力和福祉丧失能力并影响其福祉。这些研究将有助于我们理解应激对子宫内膜异位症潜在的病理生理机制的影响，以及其疼痛症状的恶化，并有助于实施应激管理干预作为治疗目标的可能性。