The effects of aging on experimental models of pain inhibition and facilitation

衰老对疼痛抑制和促进实验模型的影响

• 批准号: 8238514
• 负责人: JOSEPH L RILEY
• 金额: $ 52.32万
• 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: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8238514
• 关键词: Accounting; Adrenal Glands; Adult; Age; Aging; Area; Behavioral; Biological Markers; Biological Markers; Blood Pressure; Complex; Data; Diffuse; Elderly; Emotions; Endorphins; Enrollment; Environment; Experimental Models; Frequencies; Functional disorder; Goals; Heating; Human; Hydrocortisone; Hypothalamic structure; Immunologic Markers; Incidence; Individual; Interview; Laboratories; Laboratory Finding; Laboratory Study; Life; Longevity; Measures; Mediating; Mediator of activation protein; Methods; Modeling; Outcome; Pain; Pain Measurement; Patients; Persistent pain; Persons; Phase; Pituitary Gland; Population; Process; Protocols documentation; Proxy; Psychophysiology; Psychosocial Factor; Public Health; Quality of life; Research; Risk; Sampling; Series; Site; Sleep; Stimulus; Stress; System; Techniques; Telephone Interviews; Temperature; Testing; Time; Translating; age difference; age effect; age group; age related; biopsychosocial; central sensitization; chronic pain; clinically relevant; cohort; diffuse noxious inhibitory control; disability; electronic data; experience; human subject; intense pain; novel; pain inhibition; psychosocial; response

DESCRIPTION (provided by applicant): Older adults are at increased risk to develop prolonged pain and experience greater pain-related loss of physical and psychosocial function compared to younger cohorts. We propose that changes in endogenous pain modulatory capacity accounts for increased incidence of pain and disability in older adults. That endogenous pain modulation dysfunction is related to persistent pain is supported by a number of studies comparing chronic pain patients with healthy controls using a "pain-inhibition-by-pain" experimental model. Although this research group (and others) has shown age deficiencies using the "pain inhibits pain" model, other human laboratory models that are known to engage pain modulatory systems have not been tested across the lifespan, each potentially involving different mechanisms. The overarching goal of the proposed research is to characterize age-related changes in pain inhibitory and facilitatory function and to investigate the biopsychosocial mediators and clinical relevance of these changes. Our preliminary data suggest that sophisticated psychophysical methods reflecting net inhibitory or facilitatory effects are sensitive to changes across the lifespan and will provide a more comprehensive and clinically-relevant picture of changes in pain processing associated with aging. This proposed study will enroll 180 human subjects, ages 18-79, who will undergo assessment during three pain modulatory sessions at baseline. The pain modulatory tests will include inhibitory protocols; diffuse noxious controls and offset analgesia, and tests that involve pain facilitation; temporal summation, impaired decay of subthreshold pain (proxy for central sensitization), and a prolonged protocol which we have found produces greater temporal sensitization across repeated trials in older subjects. Individualized temperatures for the contact heat test stimulus will be used so that subjects experience similar, moderate levels of pain. We hypothesize that age will be associated with poorer endogenous pain inhibition from pain inhibitory protocols and increased pain from protocols that facilitate pain. A range of biopsychosocial markers will be measured that we hypothesize will mediate the association between age and variability in pain modulation. These measures include psychosocial factors (catastrophizing, sleep, stress, and negative emotions) and biological markers (blood pressure, 2-endorphin, cortisol, and other hypothalamic-pituitary- adrenal and immune markers). After establishing individual levels of pain facilitation and pain inhibition, we will assess pain during daily life and the impact of pain on quality of life using a series of telephone interviews and novel real-time electronic data capture each month for 6 months. We expect that changes in our pain modulatory tests will account for observed age differences in pain frequency, more pain intensity, number of pain sites, and in quality of life. PUBLIC HEALTH RELEVANCE: Older persons are at greater risk of developing prolonged pain, and when they do, they suffer a greater impact of pain on quality of life than younger persons. This study will employ cutting-edge pain testing techniques to test for changes in pain inhibitory capacity, which we hypothesize contribute to increased incidence of pain and disability in older adults. As a public health problem, the increase in numbers of elders expected in our nation's population in the coming decades render understand the mechanism behind increased pain among older adults a compelling area for research

描述（由申请人提供）：与年轻同伙相比，老年人有增加长期疼痛的风险和体验与疼痛相关的身体和社会心理功能的丧失。我们建议内源性疼痛调节能力的变化是老年人疼痛和残疾的发生率增加的原因。内源性疼痛调节功能障碍与持续性疼痛有关，通过许多研究，使用“按下疼痛抑制疼痛抑制”实验模型将慢性疼痛患者与健康对照组进行了比较。尽管该研究小组（和其他人）使用“疼痛抑制疼痛”模型显示了年龄缺陷，但已知可以参与疼痛调节系统的其他人类实验室模型尚未在整个寿命中进行测试，每种都可能涉及不同的机制。拟议的研究的总体目标是表征与年龄相关的疼痛抑制和促进功能的变化，并研究这些变化的生物心理社会介体和临床相关性。我们的初步数据表明，反映净抑制性或促进作用的复杂心理物理方法对整个寿命的变化敏感，并将提供与衰老相关的疼痛处理变化的更全面且临床上的更加相关的情况。这项拟议的研究将招募180名18-79岁的人类受试者，他们将在基线的三个疼痛调节性课程中进行评估。疼痛调节测试将包括抑制方案；扩散有害控制和抵消镇痛，以及涉及疼痛促进的测试；时间求和，亚阈值疼痛的衰减受损（中央敏化的代理）以及我们发现的延长方案会在较旧受试者的重复试验中产生更大的时间敏化。接触热测试刺激的个性化温度将被使用，以使受试者经历相似的，中等水平的疼痛。我们假设年龄将与疼痛抑制方案抑制较差的内源性疼痛抑制作用以及促进疼痛方案的疼痛增加有关。将测量一系列的生物心理社会标记，我们假设将介导疼痛调节年龄与变异性之间的关联。这些措施包括社会心理因素（灾难性，睡眠，压力和负面情绪）和生物学标记（血压，2-内啡肽，皮质醇和其他下丘脑 - 垂体 - 肾上腺肾上腺肾上腺和免疫标记）。在建立了单个疼痛促进和抑制疼痛的水平之后，我们将使用一系列电话采访和每月捕获新型的实时电子数据捕获在日常生活中评估疼痛对生活质量的影响，持续6个月。我们预计我们的疼痛调节测试的变化将解释观察到的疼痛频率，疼痛强度，疼痛部位数量和生活质量的年龄差异。 公共卫生相关性：老年人面临长期疼痛的风险，而当他们这样做时，与年轻人相比，他们对生活质量的影响更大。这项研究将采用尖端的疼痛测试技术来测试疼痛抑制能力的变化，我们假设这有助于增加老年人疼痛和残疾的发生率。作为一个公共卫生问题，在未来几十年中，我们国家人口中预期的长者数量增加了，了解老年人增加疼痛的机制是令人信服的研究领域