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（由申请人提供）：慢性腰痛（CLBP）影响超过20%的人口，每年的费用超过1000亿美元。CLBP患者肥胖的风险增加，这对治疗结果和心血管健康不利。然而，肥胖和CLBP之间的关联机制仍有待确定。候选人的长期目标是使用功能性脑成像（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。为了继续朝着这个目标前进，候选人提出（1）一个培训计划，以获得以下方面的专业知识：a）喂养和肥胖的神经生理学，B）高级计算脑成像数据分析技术，以及c）慢性疼痛管理和治疗的临床技能;（2）在进食、疼痛、计算神经成像和慢性疼痛临床治疗的神经生物学方面具有广泛专业知识的指导团队，以及（3）一系列神经成像和心理物理学实验，将测试一个新的假设，该假设规定与CLBP相关的神经适应增加了对暴饮暴食和肥胖的易感性。更具体地，含有糖和/或脂肪的高能量密度可口食物在我们的环境中是丰富的，并且被认为通过过度刺激大脑奖励系统而在肥胖症的日益流行中起重要作用。腹侧纹状体（VS）和内侧前额叶皮层（mPFC）是大脑奖赏系统的关键区域，在享乐感知和美味食物的摄取中发挥作用。与目前的提议至关重要的是，已知这些区域的功能在CLBP患者中受到广泛影响。在 此外，初步数据显示CLBP患者对高脂肪食物和饱腹感信号的享乐感知被破坏。因此，拟议的研究使用功能磁共振成像在纵向设计，以测试是否在VS-mPFC电路的改变与（1）破坏享乐反应可口的食物和饱腹感信号在新诊断的背痛患者（疼痛持续时间6-12周）过渡到CLBP的人与未过渡到CLBP的人（疼痛持续时间> 12个月）（目标1和2），和/或（2）VS-mPFC电路的改变是否仅在疼痛在一年时变为慢性后与进食行为中断相关（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随访时的体重变化。