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导致与疼痛相关的刺激产生的残疾。 在工作中受伤，虽然这种期望的神经科学还不清楚。人类的条件期望 可以通过由一系列视觉条件刺激组成的协议产生，其中一些是成对的 (CS+）与疼痛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：当激光跟随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，而前者则是 与逃避当前疼痛而不是接近疼痛有关，例如不依从物理治疗， 引起一些痛苦。回避或逃避行为的增加与以下情况的发生有关， 从骨关节炎到纤维肌痛的慢性疼痛综合征的结果。 我们建议通过直接记录局部场电位（LFP）来研究这两个领域， 大脑中参与这两个领域的成分对疼痛的预期。初步数据显示， LFP激活（ERPs事件相关电位和ERS/ERD -振荡功率的增加/减少） 杏仁核（AMY）、海马形成和部分扣带皮层对未配对CS+和 US，它可以介导条件反射并产生条件反应（CR）。预期CR包括 增加：自主活动（皮肤电导反应，SCR），以及 CS+和US，以及刺激产生的CS不愉快和注意力（凸显性）。的经验 US是痛苦的，不像CS，与条件反射有关，但与CS不愉快或突出无关， 与两个独立的结构域的存在相一致。CS SCR与ERS/ERD和ERC相关， 与CS+ US相关的频带和分量不同的频带和分量的功能 关联，反过来，与CS不愉快和CS显著性相关的那些不同。模型 这些数据表明了每个领域的网络，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。这两个模型共享包括AMY内的核在内的组件， 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 在一个结构内或相邻结构内存在组件的局部网络中， 结构.我们的前提是，这些模型中的组件将参与疼痛和条件反射过程， 并将与两个域之一相关的激活显示为单独的组件或本地网络的一部分， 将显示定义该域的分布式分层网络的交互。 这项研究可能会建议在药物开发和手术或刺激治疗的兴趣点， 疼痛综合征与显着的疼痛恐惧，如神经活动的研究，导致了网络模型的 基底神经节，提出了治疗靶点，并改变了运动障碍的治疗。