Neural Mechanism of Obesity in Chronic Low Back Pain

描述（由申请人提供）：慢性腰痛（CLBP）影响超过20%的人口，每年花费超过1000亿美元。CLBP患者发生肥胖的风险增加，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脑成像（fMRI）和心理物理工具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)慢性疼痛管理和治疗的临床技能；(2)一个在喂养、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；(3)一系列神经成像和心理物理实验，将检验一个新的假设，即与CLBP相关的神经适应增加了对暴饮暴食和肥胖的易感性。更具体地说，含有糖和/或脂肪的高能量密度美味食物在我们的环境中大量存在，人们认为，通过过度刺激大脑奖励系统，高能量密度美味食物在肥胖症日益流行的过程中发挥了重要作用。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，在快乐感知和美味食物的摄入中发挥作用。与目前的建议关键相关的是，已知这些区域的功能在CLBP患者中受到广泛影响。在

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.