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: 8723720
• 负责人: JOSEPH L RILEY
• 金额: $ 53.84万
• 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 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723720
• 关键词: Accounting; Adrenal Glands; Adult; Age; Aging; Area; Behavioral; 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; Pain intensity; Patients; Persistent pain; Persons; Phase; Pituitary Gland; Population; Process; Protocols documentation; Proxy; Psychophysics; 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.

描述（由申请人提供）：与年轻人相比，老年人发展为长期疼痛的风险增加，并且经历更大的与疼痛相关的身体和心理功能丧失。我们认为内源性疼痛调节能力的变化是老年人疼痛和残疾发生率增加的原因。内源性疼痛调节功能障碍与持续疼痛有关，这一观点得到了许多研究的支持，这些研究使用“疼痛-疼痛抑制”实验模型将慢性疼痛患者与健康对照进行了比较。尽管这个研究小组（和其他研究小组）使用“疼痛抑制疼痛”模型显示了年龄缺陷，但其他已知涉及疼痛调节系统的人类实验室模型尚未在整个生命周期中进行测试，每个模型都可能涉及不同的机制。提出的研究的总体目标是表征疼痛抑制和促进功能的年龄相关变化，并调查这些变化的生物心理社会介质和临床相关性。我们的初步数据表明，反映净抑制或促进效应的复杂心理物理方法对整个生命周期的变化很敏感，并将提供与衰老相关的疼痛处理变化的更全面和临床相关的图像。该研究将招募180名年龄在18-79岁之间的受试者，他们将在基线的三个疼痛调节阶段接受评估。疼痛调节试验将包括抑制方案；弥漫性毒性对照和抵消性镇痛，以及涉及疼痛促进的试验；时间累积，阈下疼痛的受损衰减（中枢敏化的代理），以及我们发现在老年受试者重复试验中产生更大的时间敏化的延长方案。接触热测试刺激的个性化温度将被使用，以便受试者体验相似的，中等程度的疼痛。我们假设年龄将与疼痛抑制方案中较差的内源性疼痛抑制和促进疼痛的方案中增加的疼痛有关。一系列的生物心理社会标记将被测量，我们假设将介导年龄和疼痛调节变异性之间的关联。这些测量包括社会心理因素（灾难、睡眠、压力和负面情绪）和生物标记（血压、2-内啡肽、皮质醇和其他下丘脑-垂体-肾上腺和免疫标记）。在确定个体疼痛促进和疼痛抑制水平后，我们将在6个月内每月使用一系列电话访谈和新颖的实时电子数据采集来评估日常生活中的疼痛以及疼痛对生活质量的影响。我们期望我们的疼痛调节测试的变化能够解释在疼痛频率、疼痛强度、疼痛部位数量和生活质量方面观察到的年龄差异。