Neural Mechanism of Obesity in Chronic Low Back Pain

肥胖与慢性腰痛的神经机制

• 批准号: 8843824
• 负责人: Paul Geha
• 金额: $ 18.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843824
• 关键词: Affect; Area; Back Pain; Behavior; Body Weight Changes; Body mass index; Brain; Brain imaging; Brain region; Carbohydrates; Cardiovascular system; Chronic; Chronic Phase; Chronic low back pain; Clinical Skills; Clinical Treatment; Data; Data Analyses; Early identification; Environment; Exhibits; Fatty acid glycerol esters; Feeding behaviors; Food; Functional Magnetic Resonance Imaging; General Population; Goals; Health; Hormones; Hyperphagia; Individual; Ingestion; Intake; Measures; Medial; Mediating; Mentors; Metabolic; Neurobiology; Newly Diagnosed; Nutrient; Obesity; Pain; Patients; Perception; Persistent pain; Physical activity; Play; Population; Predisposition; Prefrontal Cortex; Prevalence; Preventive Intervention; Property; Psychophysics; Research; Rest; Rewards; Risk; Role; Satiation; Signal Transduction; Societies; Staging; System; Techniques; Testing; Training; Treatment outcome; Variant; Ventral Striatum; Weight Gain; base; behavior measurement; cardiovascular health; chronic pain; cost; feeding; follow-up; hedonic; longitudinal design; neural correlate; neuroadaptation; neurobiological mechanism; neuroimaging; neuromechanism; neurophysiology; novel; obesity risk; relating to nervous system; research study; response; sugar; tool

DESCRIPTION (provided by applicant): Chronic low-back pain (CLBP) affects more than 20% of the population with an annual cost of more than a $100 billion dollar. CLBP patients are at increased risk for obesity which is detrimental to treatment outcome and cardiovascular health. However, the mechanism(s) for the association between obesity and CLBP is still to be determined. The candidate's long-term goal is to determine the neurobiological mechanisms that explain the interaction of chronic pain and obesity using functional brain imaging (fMRI) and psychophysical tools. To continue his progress towards this goal the candidate proposes (1) a training plan to gain expertise in: a) the neurophysiology of feeding and obesity, b) advanced computational brain imaging data analyses techniques, and c) clinical skills in the management and treatment of chronic pain; (2) a mentoring team with extensive expertise in the neurobiology of feeding, pain, computational neuroimaging, and clinical treatment of chronic pain, and (3) a sequence of neuroimaging and psychophysical experiments that will test a novel hypothesis stipulating that neural adaptations associated with CLBP increases susceptibility to overeating and obesity. More specifically, high energy-dense palatable foods containing sugar and/or fat are abundant in our environment and are thought to play an important role in the increasing prevalence of obesity by over- stimulating the brain reward system. The ventral striatum (VS) and medial prefrontal cortex (mPFC) are key regions of the brain reward system that play a role in hedonic perception and ingestion of palatable food. Of critical relevance to the current proposal, it is known that the function of these areas is extensively affected in CLBP patients. In addition, preliminary data shows disrupted hedonic perception of high fat food and satiety signals in CLBP patients. Therefore the proposed research uses fMRI in a longitudinal design to test whether alteration in VS-mPFC circuitry is associated with (1) disrupted hedonic responses to palatable food and satiety signaling in newly diagnosed back pain patients (pain duration 6-12 weeks) who do vs. those who do not transition to CLBP (pain duration > 12 months) (aims 1 and 2), and/or (2) whether alteration in VS-mPFC circuitry correlates to disrupted feeding behavior only after pain becomes chronic at one year (aim 3). We will also determine if these brain and behavioral measures predict weight change in newly diagnosed back pain patients at one year follow-up.

描述(申请人提供)：慢性腰背痛(CLBP)影响超过20%的人口，每年的成本超过1000亿美元。CLBP患者患肥胖症的风险增加，这对治疗结果和心血管健康都是有害的。然而，肥胖与慢性BP之间的联系机制(S)仍有待确定。这位候选人的长期目标是使用脑功能成像(FMRI)和心理物理工具来确定解释慢性疼痛和肥胖相互作用的神经生物学机制。为了继续朝着这一目标前进，候选人提出了(1)培训计划，以获得以下方面的专业知识：a)进食和肥胖的神经生理学，b)先进的计算脑成像数据分析技术，以及c)管理和治疗慢性疼痛的临床技能；(2)一个在进食、疼痛、计算神经成像和慢性疼痛的临床治疗方面拥有广泛专业知识的指导团队；以及(3)一系列神经成像和心理物理实验，以检验一项新的假设，该假说规定与CLBP相关的神经适应会增加暴饮暴食和肥胖的易感性。更具体地说，含有糖和/或脂肪的高能量密度可口食物在我们的环境中大量存在，人们认为这些食物通过过度刺激大脑奖励系统，在肥胖症的日益流行中发挥了重要作用。腹侧纹状体(VS)和内侧前额叶皮质(MPFC)是大脑奖励系统的关键区域，在享乐知觉和美味食物的摄取中发挥作用。与目前的建议密切相关的是，众所周知，这些区域的功能在CLBP患者中受到广泛影响。在……里面 此外，初步数据显示，CLBP患者对高脂肪食物和饱腹感的享乐主义感知中断。因此，这项拟议的研究在纵向设计中使用功能磁共振成像来测试VS-mPFC回路的变化是否与(1)新诊断的背痛患者(疼痛持续6-12周)与没有过渡到CLBP(疼痛持续时间12个月)(目标1和2)的新诊断的背痛患者对美味食物和饱腹感信号的享乐反应中断有关，和/或(2)VS-mPFC回路的变化是否仅在疼痛变成慢性疼痛一年后才与喂养行为中断相关(目标3)。我们还将确定这些大脑和行为测量是否可以预测新诊断的背痛患者在一年的随访中的体重变化。