Non-esterified Fatty Acids and Chronic Pain in Older Adults

非酯化脂肪酸与老年人的慢性疼痛

基本信息

批准号：
10615367
负责人：
KENNETH Jay MUKAMAL
金额：
$ 15万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615367
关键词：
Aging Anatomy Attention Award Back Black race Blood - brain barrier anatomy Brain Cardiovascular Diseases Cardiovascular system Chronic Cohort Studies Collection Communities Data Degenerative polyarthritis Dementia Development Diabetes Mellitus Diagnosis Elderly Epidemic Evaluation Event Fatty acid glycerol esters Funding Future Gait Hand Health system Heart Diseases Hospitalization Human Impairment Inpatients Link Lower Extremity Malignant Neoplasms Measurement Measures Medical Memory Mentors Metabolic Metabolic Marker Metabolism Mid-Career Clinical Scientist Award (K24)Musculoskeletal National Heart, Lung, and Blood Institute Neurocognitive Neurologic Neurons Obesity Observational Study Older Population Outcome Pain Pain Measurement Pain management Parents Participant Pathway interactions Patient Self-Report Peripheral Peripheral Nerves Persons Pharmacology Phenotype Play Population Prevalence Process Psyche structure Reporting Research Research Personnel Resources Risk Role Site Source Supporting Cell Syndrome Time Underrepresented Minority Visit Weight Weight-Bearing state age related base cardiovascular health chronic pain clinical pain cost disability economic cost epidemiology study falls follow-up foot frailty functional independence functional loss inpatient service insight interest minority investigator opioid overdose prevent prospective sugar vibration years lived with disability

项目摘要

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.

疼痛是老年人中令人难以置信的常见，朴实的和棘手的问题。它存在于某些三分之二的老年人（随着时间的流逝，患病率都在增加），可以预测功能独立性的丧失，与收集和跌倒受损有关，关注和记忆的干扰，据估计有一个 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经济成本。鉴于慢性疼痛在老年人中产生了深远的影响，以及治疗不良的选择，更好了解其决定者至关重要。肥胖症长期以来一直被认为是老年人群的慢性疼痛，但其机制尚不确定。虽然肥胖与痛苦的联系通常归因于与慢性超重有关的骨关节炎，肥胖不仅与背部和脚等承重部位的疼痛，即使有手的疼痛。这些观察表明这种肥胖具有不良的代谢作用，导致慢性疼痛远远超出了纯粹的体重。在肥胖的代谢作用中，较高水平的非层化脂肪酸（NEFA）特别有意义。 NEFA穿过血脑屏障，对神经元和支持细胞都有毒性。在以前的分析中心血管健康研究（CHS），我们已经表明，循环水平与残疾和流动性限制以及精神，神经系统和肌肉骨骼的可能性更高住院。这些关联都表明NEFA可以在调节疼痛中发挥作用。迄今为止，但是，尚未评估NEFA与疼痛的形式关系。我们建议使用富人 CHS中的数据库，以评估这种关系的三个潜在方面 - 与自我的关联报道了疼痛，国家疼痛策略示诊断的主张以及周围神经功能。 CHS是一项正在进行的队列研究，对来自四个美国社区的老年人进行了研究 1989-1990至1998-1999，并继续遵循残疾，心血管事件和医疗主张。在以前的NHLBI资助奖中，我们在> 4,000名参与者中测量了NEFA水平（以及NIA 资金，在稍后的约2,000名参与者中重复进行测量。此外，CHS非常丰富，但是目前未充分利用的，我们建议在此补充剂中利用慢性疼痛的潜在数据。这些数据包括对7个指定解剖部位的疼痛的重复评估（和一个开放式的选项），CMS索赔非卧床和住院服务，以及较低的振动意义的测量四肢。这些来源共同提供了丰富的，全面的探讨和痛苦。由于NEFA在药品上可能是可修改的，因此我们的结果可能会提供定性的新见解进入预防，减轻或调节老年人疼痛的方式。这种补充也将使第一次简化了研究CHS疼痛的过程，使Mukamal博士和The Mukamal博士的月经受益整个研究，并将支持承诺的年轻代表性不足的少数群体调查员Ahiawodzi博士。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Associations between alcohol consumption and hepatic steatosis in the USA.

DOI：
10.1111/liv.15020
发表时间：
2021-09
期刊：
LIVER INTERNATIONAL
影响因子：
6.7
作者：
Niezen, Sebasian;Trivedi, Hirsh D.;Mukamal, Kenneth J.;Jiang, Zhenghui G.
通讯作者：
Jiang, Zhenghui G.

Pharmacist-led rapid medication titration for hypertension management by telehealth: A quality improvement initiative.

药剂师主导的远程医疗高血压管理快速药物滴定：一项质量改进举措。

DOI：
10.1111/jch.14750
发表时间：
2024
期刊：
Journal of clinical hypertension (Greenwich, Conn.)
影响因子：
0
作者：
Ishak,AnthonyM;Mukamal,KennethJ;Wood,JuliaM;Vyavahare,Medha;Cluett,JenniferL;Juraschek,StephenP
通讯作者：
Juraschek,StephenP

Intake and Sources of Dietary Fiber, Inflammation, and Cardiovascular Disease in Older US Adults.

DOI：
10.1001/jamanetworkopen.2022.5012
发表时间：
2022-03-01
期刊：
JAMA network open
影响因子：
13.8
作者：
Shivakoti R;Biggs ML;Djoussé L;Durda PJ;Kizer JR;Psaty B;Reiner AP;Tracy RP;Siscovick D;Mukamal KJ
通讯作者：
Mukamal KJ

Dietary Macronutrients and Circulating Nonesterified Fatty Acids: A Secondary Analysis of the OMNI Heart Crossover Trial.

膳食大量营养素和循环非酯化脂肪酸：OMNI 心脏交叉试验的二次分析。