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

描述(由申请人提供)：与年轻人群相比，老年人发展为长期疼痛的风险增加，并经历更大的与疼痛相关的身体和心理社会功能丧失。我们认为，内源性疼痛调节能力的改变是老年人疼痛和残疾发生率增加的原因。内源性疼痛调制功能障碍与持续性疼痛有关，这一观点得到了许多研究的支持，这些研究使用“疼痛抑制”的实验模型对慢性疼痛患者和健康对照组进行了比较。尽管这个研究小组(和其他研究小组)已经使用“疼痛抑制疼痛”模型显示了年龄缺陷，但其他已知的使用疼痛调制系统的人类实验室模型还没有在整个生命周期内进行测试，每个模型都可能涉及不同的机制。这项研究的主要目标是描述与年龄相关的疼痛抑制和促进功能的变化，并调查这些变化的生物、心理和社会介质及其临床相关性。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景。这项拟议的研究将招募180名年龄在18-79岁的人类受试者，他们将在基线的三次疼痛调节会议期间接受评估。疼痛调制测试将包括抑制方案；扩散伤害性控制和抵消止痛，以及涉及疼痛促进的测试；时间总和，阈值下疼痛的受损衰减(中枢敏化的替代)，以及我们发现在老年受试者重复试验中产生更大时间敏感化的延长方案。接触热测试刺激的个性化温度将被使用，以便受试者体验类似的中等程度的疼痛。我们假设，年龄将与疼痛抑制方案的内源性疼痛抑制较差和促进疼痛的方案增加的疼痛有关。我们将测量一系列生物、心理和社会标志物，我们假设这些标志物将在年龄和疼痛调制的可变性之间起中介作用。这些测量包括心理社会因素(灾难、睡眠、压力和负面情绪)和生物标记物(血压、2-内啡肽、皮质醇和其他下丘脑-垂体-肾上腺和免疫标记物)。在建立了个人的疼痛促进和疼痛抑制水平后，我们将使用一系列电话采访和新颖的实时电子数据采集，在6个月的时间里评估日常生活中的疼痛以及疼痛对生活质量的影响。我们预计疼痛调节测试的变化将解释观察到的疼痛频率、更多疼痛强度、疼痛部位数量和生活质量的年龄差异。

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.