Neural Mechanism of Obesity in Chronic Low Back Pain

肥胖与慢性腰痛的神经机制

基本信息

批准号：
9455634
负责人：
Paul Geha
金额：
$ 17.26万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
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/9455634
关键词：
Affect Area Back Pain Behavior Body Weight Changes Body mass index Brain Brain imaging Carbohydrates Cardiovascular system Chronic Chronic Phase Chronic low back pain Clinical Skills Clinical Treatment Data Data Analyses Desire for food Early identification Environment Exhibits Fatty acid glycerol esters Feeding behaviors Food General Population Goals Hyperphagia Individual Ingestion Intake Measures Medial Mediating Mentors Metabolic Metabolic hormone Neurobiology Newly Diagnosed Nutrient Obesity Pain Pain management Palate 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 System Techniques Testing Training Treatment outcome Ventral Striatum Weight Gain base behavior measurement brain reward regions cardiovascular health chronic pain chronic pain patient cost experimental study feeding follow-up hedonic individual variation longitudinal design neural correlate neuroadaptation neurobiological mechanism neuroimaging neuromechanism neurophysiology novel obesity risk pain patient public health relevance relating to nervous system response sugar tool

项目摘要

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，每年造成的损失超过 1000 亿美元。 CLBP 患者肥胖的风险增加，这不利于治疗结果和心血管健康。然而，肥胖与 CLBP 之间的关联机制仍有待确定。候选人的长期目标是利用功能性脑成像 (fMRI) 和心理物理学工具确定解释慢性疼痛和肥胖之间相互作用的神经生物学机制。为了继续实现这一目标，候选人提出 (1) 一项培训计划，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) 先进的计算脑成像数据分析技术，以及 c) 管理和治疗方面的临床技能慢性疼痛； (2) 一个在进食、疼痛、计算神经影像学和慢性疼痛临床治疗等神经生物学方面拥有丰富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学实验，这些实验将检验一个新的假设，该假设规定，神经适应与CLBP 会增加暴饮暴食和肥胖的可能性。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，并且被认为通过过度刺激大脑奖励系统而在肥胖患病率增加中发挥重要作用。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，在享乐感知和美味食物的摄入中发挥作用。与当前的提议至关重要的是，已知 CLBP 患者这些区域的功能受到广泛影响。在此外，初步数据显示 CLBP 患者对高脂肪食物的享乐感知和饱腹感信号受到干扰。因此，拟议的研究在纵向设计中使用 fMRI 来测试 VS-mPFC 电路的改变是否与 (1) 新诊断背痛患者（疼痛持续时间 6-12 周）对美味食物和饱腹感信号的享乐反应中断相关。与未过渡到 CLBP 的患者（疼痛持续时间 > 12 个月）（目标 1 和 2），和/或 (2) VS-mPFC 电路的改变是否与中断相关仅在疼痛成为慢性一年后才进行进食行为（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背痛患者一年随访时的体重变化。