Examining the Role of Central Sensitization with Aging: an Investigation of Older Adults with and without Chronic Low Back Pain

项目摘要/摘要 在美国，慢性疼痛每年影响着500多万老年人。这一负担预计将 鉴于一般人口正在老龄化，慢性疼痛的患病率在未来几年会进一步恶化。 在老年人中很高，而且尚不清楚为什么衰老是慢性疼痛障碍的风险因素。《国家报》 老龄问题研究所敏锐地意识到这一僵局，要求将研究重点放在 “阐明疼痛体验的潜在机制及其在衰老中的后果”。文学有 已确立的中枢神经系统敏感化(称为中枢敏感化)是一种损害， 放大患有慢性疼痛的年轻人和中年人的疼痛感知，导致疼痛持续和 由此导致的残疾。然而，很少有研究评估中央银行的存在和后果。 在老年慢性疼痛条件下的敏化，包括慢性下腰痛。这种知识上的差距是 由于缺乏对中枢敏感化是否随着年龄的增长而发生的理解，以及缺乏这种情况，使情况更加复杂 中枢敏感化的明确诊断标准。因此，这项提议的目的是澄清是否 以及作为生物老化的结果，中枢敏感化是如何发展的，并表征了存在和 中枢敏感化对患有慢性下腰痛的老年人的临床意义。在目标1中，我们将 确定患有慢性下腰痛的老年人在多大程度上表现出静态和 与没有慢性疼痛的老年人和年轻人相比，动态疼痛敏感性。对于目标2，我们将量化 这三组之间在实验诱导的敏化方面的差异。在目标3中，我们将研究 中枢敏感化指标与临床疼痛、身体功能和运动功能的关系 患有慢性下腰痛的老年人的可感知残疾。这项提议的中心假设是 患有慢性腰背痛的老年人将表现出最大程度的中枢敏感化， 这将与更大的临床疼痛强度，更差的身体功能和更差的感觉有关 残疾。这些结果有可能为一级、二级和三级预防工作提供信息 确定CS是否发生生物老化，结合标准和标准优化CS的鉴定 新的测量方法，并为潜在的可修改的 分别是造成老年人慢性腰痛负担的机制。这项提议是至关重要的第一步 朝着奖学金申请者的长期目标迈进一步，那就是提高小学、中学和高等教育水平 通过量化和干预机制为易受伤害的慢性疼痛人群提供预防 (如CS)，这是不适应疼痛敏感性的基础。此外，这项奖学金提案将提供 接受具有老年学、疼痛科学和康复专业知识的导师的系统培训的申请者； 这项培训不仅将有助于完成这项研究项目，而且还将为申请者准备 作为一名多产的临床科学家的职业生涯。

PROJECT SUMMARY/ABSTRACT Chronic pain affects over 5 million older adults every year in the United States. This burden is expected to worsen in the coming years given that the general population is aging, chronic pain prevalence is inordinately high among older adults, and it is unknown why aging is a risk factor for chronic pain disorders. The National Institute on Aging is keenly aware of this impasse, as evidenced by requests for research to focus on the “elucidation of mechanisms underlying pain experience and its consequences in aging”. Literature has established sensitization of the central nervous system (termed central sensitization) as an impairment that amplifies pain perception in young and middle aged adults with chronic pain, leading to pain persistence and resultant disability. However, a paucity of research has evaluated the presence and consequences of central sensitization in geriatric chronic pain conditions, including chronic low back pain. This gap in knowledge is further complicated by a lack of understanding whether central sensitization occurs with aging, and an absence of definitive diagnostic criteria for central sensitization. Therefore, the goals of this proposal are to elucidate if and how central sensitization develops as a result of biological aging, and characterize the presence and clinical implications of central sensitization in older adults with chronic low back pain. In Aim 1, we will determine the extent to which older adults with chronic low back pain demonstrate increased static and dynamic pain sensitivity compared to older and younger adults without chronic pain. For Aim 2, we will quantify differences in experimentally-induced sensitization between these three groups. In Aim 3, we will examine the relationship between indicators of central sensitization and clinical measures of pain, physical function and perceived disability among older adults with chronic low back pain. The central hypothesis of this proposal is that older adults with chronic low back pain will demonstrate the greatest magnitude of central sensitization, which will be associated with greater clinical pain intensity, poorer physical function, and worse perceived disability. The results have the potential to inform primary, secondary and tertiary prevention efforts by determining if CS occurs with biological aging, optimizing the identification of CS by combining standard and novel measurement methodologies, and providing foundational evidence for a potentially modifiable mechanism that burdens older adults with chronic low back pain, respectively. This proposal is a critical first step towards the long-term goal of this fellowship applicant, which is to improve primary, secondary and tertiary prevention efforts for vulnerable chronic pain populations by quantifying and intervening upon mechanisms (such as CS) that underlie maladaptive pain sensitivity. Additionally, this fellowship proposal will provide the applicant with structured training from mentors with expertise in gerontology, pain science and rehabilitation; this training will not only facilitate completion of this research project, but also prepare the applicant for a career as a productive clinician scientist.