Neural Mechanism of Obesity in Chronic Low Back Pain

肥胖与慢性腰痛的神经机制

• 批准号: 8679716
• 负责人: Paul Geha
• 金额: $ 18.27万
• 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/8679716
• 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; chronic pain; cost; feeding; follow-up; hedonic; longitudinal design; neuroadaptation; neurobiological mechanism; neuroimaging; neuromechanism; neurophysiology; novel; obesity risk; public health relevance; 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（由申请人提供）：慢性低背痛（CLBP）影响超过20％的人口，每年成本超过1000亿美元。 CLBP患者的肥胖风险增加，这对治疗结果和心血管健康有害。但是，肥胖与CLBP之间关联的机制仍有待确定。候选人的长期目标是确定使用功能性脑成像（fMRI）和心理物理工具来解释慢性疼痛和肥胖相互作用的神经生物学机制。为了继续他朝着这一目标的进步，候选人提出（1）培训计划，以获得以下方面的专业知识： （2）在喂养，疼痛，计算神经影像学和临床治疗慢性疼痛的神经生物学方面具有广泛专业知识的指导团队，以及（3）一系列神经影像学和心理物理实验的顺序，这些序列将检验一种新型的假设，该假设与CLBP相关的神经适应性增加了与Clbp相关的神经适应性。更具体地说，在我们的环境中，含糖和/或脂肪的高能量浓密的可口食品很丰富，被认为通过过度刺激脑奖励系统，在肥胖症的日益普及中起着重要作用。腹侧纹状体（VS）和内侧前额叶皮层（MPFC）是大脑奖励系统的关键区域，在享乐感和摄入可口食品中发挥作用。与当前建议的关键相关性，众所周知，这些区域的功能在CLBP患者中受到广泛影响。在 此外，初步数据表明，CLBP患者对高脂食品和饱腹感信号的享乐主义受到了干扰。 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电路仅在疼痛在一年后慢性后才与破坏的喂养行为相关（AIM 3）。我们还将确定这些大脑和行为措施是否可以预测新诊断的背痛患者的体重变化，一年随访。