Human Networks for Behaviors related to the Expectation of Pain

与疼痛预期相关的行为的人类网络

• 批准号: 10320934
• 负责人: Fred Lenz
• 金额: $ 59.97万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320934
• 关键词: Amygdaloid structure; Anatomy; Anterior; Anxiety; Attention; Basal Ganglia; Behavior; Biological Assay; Brain; Cell Nucleus; Clinical; Conditioned Reflex; Coping Skills; Cues; Data; Degenerative polyarthritis; Environment; Epilepsy; Etiology; Event; Event-Related Potentials; Fibromyalgia; Frequencies; Fright; Functional Magnetic Resonance Imaging; Future; Galvanic Skin Response; Hippocampal Formation; Human; Implanted Electrodes; Individual; Injury; Insula of Reil; Intractable Epilepsy; Lasers; Lateral; Lead; Measures; Mediating; Modeling; Movement Disorders; Neuronal Plasticity; Neurons; Neurosciences; Occupations; Operative Surgical Procedures; Outcome; Pain; Pain management; Personality; Physical therapy; Physiologic pulse; Placebo Effect; Prefrontal Cortex; Process; Protocols documentation; Resolution; Role; Safety; Seizures; Signal Transduction; Site; Stimulus; Structure; Study models; Syndrome; System; Testing; Training; Visual; base; chronic pain; cingulate cortex; clinical pain; conditioning; disability; drug development; expectation; experience; interest; network models; new therapeutic target; non-compliance; pain processing; pain-related disability; relating to nervous system; research clinical testing; response; therapeutic target; visual stimulus

The conditioned expectation or fear of pain often results in disability produced by stimuli related to a painful injury on the job, although the neuroscience of this expectation is unclear. Conditioned expectation in humans can be produced by a protocol that consists of a train of visual conditioning stimuli, some of which are paired (CS+) with a painful laser pulse unconditioned stimulus (US). We now propose to use this protocol to study two domains of this expectation: the experience of pain produced by the laser when it follows the CS+, and the anticipation of pain produced by the CS+. The latter is related to avoidance of future pain and the former is related to escape from current pain instead of approach, e.g. noncompliance with physical therapy which can cause some pain. Increases in either avoidance or escape behaviors are related to occurrence of, and worse outcomes in, chronic pain syndromes from osteoarthritis to fibromyalgia. We propose to study the two domains by recording local field potentials (LFP) directly from anatomic components in the brain involved in these two domains for the expectation of pain. Our Preliminary Data shows LFP activations (ERPs Event Related Potentials & ERS/ERD - increases/ decreases in oscillatory power) in the Amygdala (AMY), Hippocampal formation and parts of the cingulate cortex in response to the unpaired CS+ and US, which may mediate conditioning and produce Conditioned Responses (CRs). CRs for anticipation include increases in: autonomic activity (Skin Conductance Response, SCR), and in ratings of the association between the CS+ and US, and CS unpleasantness and attention produced by a stimulus (salience). The experience of the US was painful, unlike the CS, and was related to conditioning but not to CS unpleasantness or salience, which is consistent with the presence of two separate domains. The CS SCR was related to ERS/ERD and ERC as a function of both frequency bands and components which were different from those related to the CS+ US association which, in turn, were different from those related to CS unpleasantness and CS salience. Model networks for each domain are suggested by these Data, and are supported by the evidence of studies of anatomic projections and fMRI signals. These two models share components including nuclei within the AMY, Anterior and Mid-Cingulate, but differ in components of the Hippocampal formation, Insula, and Lateral Prefrontal Cortex, and in Local networks defined by the presence of of components within one structure or within adjacent structures. Our premise is that components in these models will be involved in pain and conditioning processes, and show activations related to one of the two domains as individual components or as part of Local Network, and will show interactions that define a distributed, Hierarchical network for that domain. This study may suggest sites of interest in drug development and in surgical or stimulation therapies for pain syndromes with significant fear of pain, like studies of neural activity that led to a network model of the basal ganglia, which suggested therapeutic targets and transformed the treatment of Movement Disorders.

对疼痛的条件性期望或恐惧通常会导致与疼痛相关的刺激所产生的残疾。 工作中受伤，尽管这种期望的神经科学尚不清楚。人类的条件期望 可以通过由一系列视觉调节刺激组成的协议产生，其中一些刺激是配对的 (CS+) 使用痛苦的激光脉冲无条件刺激 (US)。我们现在建议使用该协议来研究两个 这种期望的领域：激光跟随 CS+ 时产生的疼痛体验，以及 对 CS+ 产生的疼痛的预期。后者与避免未来的痛苦有关，而前者则与避免未来的痛苦有关。 与逃避当前的痛苦而不是接近有关，例如不遵守物理治疗可能会 造成一些疼痛。回避或逃避行为的增加与更糟糕的情况的发生有关 结果是，从骨关节炎到纤维肌痛的慢性疼痛综合征。 我们建议通过直接从解剖记录局部场电位（LFP）来研究这两个领域 大脑中涉及这两个区域的成分用于预期疼痛。我们的初步数据显示 LFP 激活（ERP 事件相关电位和 ERS/ERD - 振荡功率的增加/减少） 杏仁核 (AMY)、海马结构和部分扣带皮层对未配对的 CS+ 和 US，它可以调节调节并产生条件反应（CR）。预期的 CR 包括 自主活动（皮肤电导反应，SCR）以及之间关联的评级增加 CS+ 和 US，以及刺激（显着性）产生的 CS 不愉快和注意力。的经验 与 CS 不同，US 是痛苦的，并且与条件反射有关，但与 CS 的不愉快或显着性无关，这是 与两个独立域的存在一致。 CS SCR 与 ERS/ERD 和 ERC 相关 与 CS+ US 相关的频段和组件的功能不同 反过来，这种关联又不同于与 CS 不愉快和 CS 显着性相关的关联。模型 这些数据建议了每个领域的网络，并得到了以下研究证据的支持 解剖投影和功能磁共振成像信号。这两个模型共享组件，包括 AMY 内的原子核， 前扣带回和中扣带回，但海马结构、岛叶和外侧前额叶的组成部分不同 皮层，以及由一个结构内或相邻结构内的组件的存在定义的局部网络 结构。我们的前提是这些模型中的组件将参与疼痛和调理过程， 并将与两个域之一相关的激活显示为单独组件或本地网络的一部分，以及 将显示为该域定义分布式分层网络的交互。 这项研究可能表明药物开发和手术或刺激疗法的兴趣点 对疼痛有明显恐惧的疼痛综合症，例如对神经活动的研究，该研究产生了一个网络模型 基底神经节，它提出了治疗目标并改变了运动障碍的治疗方法。