Non-esterified Fatty Acids and Chronic Pain in Older Adults

疼痛是一个令人难以置信的常见，负担，和棘手的问题，在老年人。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， 与步态受损和福尔斯有关，干扰注意力和记忆力，据估计， 2010年，美国的经济成本约为6000亿美元-大约是心脏病和癌症的总和。 考虑到慢性疼痛对老年人的深远影响，以及治疗它的不良选择， 了解其决定因素至关重要。长期以来，肥胖一直被认为是导致 慢性疼痛在老年人群中，但其机制尚不确定。虽然肥胖与疼痛的联系 通常归因于与慢性超重有关的骨关节病，肥胖不仅与 背部和足部等承重部位疼痛，甚至手部疼痛。这些观察结果表明 肥胖对新陈代谢有不良影响，导致慢性疼痛，远远超过单纯的体重。 在肥胖的代谢影响中，较高水平的非酯化脂肪酸（NEFA）特别令人感兴趣。 NEFA穿过血脑屏障，对神经元和支持细胞都有毒性。在以前的分析中， 在心血管健康研究（CHS）中，我们已经表明NEFA的循环水平与以下因素相关： 残疾和行动受限，精神、神经和肌肉骨骼疾病的可能性更高 住院治疗这些关联都表明NEFA可能在调节疼痛中发挥作用。到目前为止， 然而，NEFA与疼痛的正式关系尚未得到评估。我们建议利用富人 CHS中的数据库来评估这种关系的三个潜在方面-与自我的关联， 报告的疼痛，国家疼痛战略推荐诊断的索赔，以及外周神经功能。 CHS是一项正在进行的队列研究，来自美国四个社区的老年人从 1989-1990年至1998-1999年，并继续随访残疾、心血管事件和医疗 索赔在之前的NHLBI资助的奖项中，我们测量了> 4，000名参与者的NEFA水平（以及NIA 在随后的访问中，在约2，000名参与者中重复测量）。此外，CHS拥有极其丰富的， 但目前未充分利用，我们建议在本补充中利用慢性疼痛的潜在数据。 这些数据包括对7个指定解剖部位疼痛的重复评估（以及一项开放式研究）。 选择），CMS要求的门诊和住院服务，以及测量振动感，在这两个较低的 四肢总之，这些来源为NEFA和疼痛提供了丰富，互补的视角。 由于NEFA是潜在的可修改的变量，我们的结果可能会提供定性的新见解 预防、减轻或调节老年人疼痛的方法。这一补充也将使 首次简化了研究CHS疼痛的流程，使Mukamal博士和 研究作为一个整体，并将支持Ahiawodzi博士，一个有前途的年轻代表性不足的少数民族调查员。

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.