Non-esterified Fatty Acids and Chronic Pain in Older Adults

在老年人中，疼痛是一个令人难以置信的常见、负担沉重和棘手的问题。它存在于一些 三分之二的老年人(患病率随着时间的推移而增加)预示着功能独立性的丧失， 与步态受损和跌倒有关，干扰注意力和记忆，据估计有 2010年，美国的经济损失约为6000亿美元--大约相当于心脏病和癌症的总和。 考虑到慢性疼痛对老年人的深刻影响，以及治疗它的糟糕选择，更好 了解其决定因素是至关重要的。长期以来，肥胖一直被认为是导致 老年人群的慢性疼痛，但其机制尚不确定。尽管肥胖与疼痛之间的联系 通常被归因于骨关节病与慢性超重有关，肥胖不仅与 背部和脚部等承重部位疼痛，甚至手部疼痛。这些观察结果表明 肥胖会对新陈代谢产生不利影响，导致慢性疼痛，而不仅仅是体重问题。 在肥胖的代谢影响中，更高水平的非酯化脂肪酸(NEFA)尤其令人感兴趣。 NEFAs可以穿过血脑屏障，对神经元和支持细胞都有毒性。在之前的分析中， 心血管健康研究(CHS)，我们已经表明循环中的NEFAs水平与 残疾和活动受限，精神、神经和肌肉骨骼疾病的可能性较高 住院治疗。所有这些关联都表明，NEFA可能在调节疼痛方面发挥作用。到目前为止， 然而，NEFAs与疼痛的正式关系尚未得到评估。我们建议利用富人 CHS中的数据仓库，以评估这种关系的三个潜在方面-与自我的关联 报告疼痛，声称国家疼痛战略-推荐的诊断，以及周围神经功能。 CHS是一项正在进行的队列研究，研究对象是来自美国四个社区的老年人，他们从 1989-1990至1998-1999，并继续因残疾、心血管事件和内科疾病而接受随访 索赔。在之前的NHLBI资助的奖项中，我们测量了4,000名参与者(以及NIA)的NEFA水平 资金，在后来访问约2,000名参与者时重复了这一衡量标准)。此外，CHS拥有极其丰富的， 但目前未得到充分利用的关于慢性疼痛的潜在数据，我们建议在本补充资料中加以利用。 这些数据包括对7个指定解剖部位的疼痛的重复评估(和无限制的 选项)，CMS对门诊和住院服务的索赔，以及在这两个较低的地区测量振动感觉 四肢。综上所述，这些来源提供了一个丰富的、互补的视角来看待不良后果和痛苦。 由于NEFA在药理上是潜在的可修改的，我们的结果可能提供定性的新见解 以预防、减轻或调节老年人的疼痛。这份补编还将使 首次简化了在CHS中研究疼痛的过程，使Mukamal博士和 作为一个整体的研究，将支持阿希亚沃兹博士，他是一位有前途的年轻的、未被充分代表的少数族裔调查员。

Pain is an incredibly common, burdensome, and intractable problem among older adults. It is present in some two-thirds of older adults (a prevalence that is increasing over time), predicts loss of functional independence, is associated with impaired gait and falls, interferes with attention and memory, and was estimated to have an economic cost in the US in 2010 of ~$600 billion – approximately that of heart disease and cancer combined. Given the profound impact of chronic pain in older adults, and the poor options for treating it, better understanding of its determinants is essential. Obesity has long been recognized as a major contributor to chronic pain in older populations, but its mechanism is uncertain. Although the association of obesity with pain is commonly attributed to osteoarthrosis related to chronic excess weight, obesity is associated not only with pain in load-bearing sites like the back and foot but even with pain of the hand. These observations suggest that adiposity has adverse metabolic effects leading to chronic pain well beyond sheer weight alone. Among metabolic effects of obesity, higher levels of non-esterified fatty acids (NEFA) are of particular interest. NEFAs cross the blood-brain barrier and are toxic to both neurons and supporting cells. In previous analyses in the Cardiovascular Health Study (CHS), we have shown that circulating levels of NEFAs are associated with disability and mobility limitation and with a higher likelihood of mental, neurologic, and musculoskeletal hospitalizations. These associations all suggest that NEFAs could have a role in modulating pain. To date, however, the formal relationship of NEFAs with pain has not been evaluated. We propose to use the rich storehouse of data in CHS to evaluate three potential aspects of this relationship – associations with self- reported pain, claims for National Pain Strategy-recommended diagnoses, and peripheral nerve function. CHS is an ongoing cohort study of older adults from four US communities who were evaluated in-person from 1989-1990 to 1998-1999 and have continued to be followed for disability, cardiovascular events, and medical claims. In a previous NHLBI-funded award, we measured NEFA levels in >4,000 participants (and with NIA funding, repeated the measurement at a later visit in ~2,000 participants). In addition, CHS has extremely rich, but currently under-utilized, potential data on chronic pain that we propose to leverage in this supplement. These data include repeated assessments of pain at 7 designated anatomical sites (and an open-ended option), CMS claims for ambulatory and inpatient services, and measurement of vibration sense in both lower extremities. Together, these sources provide a rich, complementary look into NEFAs and pain. Because NEFAs are potentially modifiable pharmacologically, our results may provide qualitative new insights into ways to prevent, reduce, or modulate pain in older adults. This supplement will also make possible for the first time a streamlined process for studying pain in CHS, benefitting both mentees of Dr. Mukamal and the study as a whole, and will support Dr. Ahiawodzi, a promising young underrepresented minority investigator.