Age-Related Differences in Psychophysical and Neurobiological Response to Pain

描述(由申请人提供)：老年人治疗不当的疼痛是一个严重的公共卫生问题。与年轻人相比，有证据表明，老年人的诊断更痛苦，疼痛的感觉阈值更高，而且有可能得不到疼痛的治疗。文献中报道了与疼痛体验的性别相关的差异，女性通常经历更多的疼痛，并报告说更敏感。治疗不当的疼痛会导致许多相关症状，对生活质量产生负面影响，并增加医疗费用。探索疼痛处理过程中变化的生物学原因 对于增加我们对老年人疼痛的理解至关重要。缺乏支持老年人最佳疼痛管理做法的神经生物学证据，使这些人面临不良疼痛管理做法的风险。这个项目的目标是确定性别和年龄相关的心理物理和神经生理学在疼痛处理过程中的差异。我们的试点数据在12名男性和12名女性(年龄匹配)健康老年人(年龄65-81岁)的样本中表明，对热痛的反应，年龄的增加与大脑激活的增加和不适感的减少有关，只有女性如此。使用心理物理学(测量感觉阈值和情感不愉快)和fMRI血氧水平依赖(BOLD)方法(测量刺激诱发的脑激活)，我们将在广泛的健康成年人(30-89岁)中检验与年龄相关的热痛处理及其潜在的神经生理学差异。我们还将获得静息状态的功能连接性数据，用于二次分析，探索静息状态连接性是否预测对热痛的心理物理和神经生理学反应。为了控制与衰老相关的血流改变的影响，我们将获得静息状态动脉自旋标记磁共振(ASL)数据来量化静息脑血流量(CBF)。我们将在提出的疼痛、衰老和性别的神经模型的背景下解释这些发现。我们的总体假设是，与年龄相关的神经系统变化会导致调节疼痛相关不适的抑制回路的变化，从而使老年人，特别是女性，在受伤时发现疼痛的风险降低，疼痛治疗不足的风险增加，慢性疼痛的风险增加。感觉和情感加工的改变对与年龄和性别相关的疼痛评估和管理策略有影响。使用功能磁共振成像评估实验性疼痛的最新进展为我们的长期目标提供了重要的基础，这些目标是确定衰老如何影响疼痛处理的心理物理学和神经生物学，并将这些信息用作未来R01研究的正常基线数据，包括患有疼痛状况的老年人，以改进预防、评估和治疗策略。

DESCRIPTION (provided by applicant): Poorly treated pain in older adults is a critical public health problem. When compared to young adults, evidence suggests that older adults have more painful diagnoses, have increased sensory thresholds for pain, and are at risk for under treatment of their pain. Sex associated differences in the experience of pain are reported in the literature with women generally experiencing more pain and reporting increased sensitivity. Poorly treated pain leads to many associated symptoms, negatively impacts quality of life, and increases health care costs. Exploring the biological reasons for alterations in pain processing is essential to increasing our understanding about pain in older adults. The paucity of neurobiological evidence to support best practice pain management in older adults places these individuals at risk for poor pain management practices. The goals of this project are to determine sex and age associated psychophysical and neurophysiological differences in the processing of pain. Our pilot data in a sample of 12 male and 12 female (age-matched) healthy older adults (ages 65-81) suggests that in response to thermal pain, increasing age is associated with increased brain activation and reduced unpleasantness only in females. Using psychophysics (to measure sensory threshold and affective unpleasantness) and fMRI blood oxygenation level dependent (BOLD) methods (to measure stimulus-evoked brain activation), we will examine age-associated differences in thermal pain processing and their underlying neurophysiology in a broad range of healthy adults (age 30-89). We will also acquire resting state functional connectivity data for secondary analyses exploring whether resting state connectivity predicts psychophysical and neurophysiological responses to thermal pain. To control for the effects of altered blood flow associated with aging, we will acquire resting state arterial spin labeling MRI (ASL) data to quantify resting cerebral blood flow (CBF). We will interpret findings in the context of a proposed neural model of pain, aging, and sex. Our overall hypothesis is that age-associated nervous system changes lead to alterations in inhibitory circuits that modulate pain associated unpleasantness which place older adults, especially females, at reduced risk for detection of pain upon injury, increased risk for under treatment of pain, and increased risk for chronic pain. Altered sensory and affective processing has implications for age-related and sex-specific pain assessment and management strategies. Recent advancements in assessing experimental pain using fMRI provide a critical foundation for our long-term goals which are to determine how aging affects the psychophysics and neurobiology of pain processing and to use this information as normal baseline data for future R01 studies including older adults with painful conditions to inform improved prevention, assessment, and treatment strategies.