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.

条件期望或对疼痛的恐惧通常会导致与痛苦有关的刺激产生的残疾 工作的伤害，尽管这种期望的神经科学尚不清楚。人类有条件的期望 可以由由一系列视觉调节刺激组成的协议产生，其中一些是配对的 （CS+）具有痛苦的激光脉冲无条件刺激（US）。我们现在建议使用该协议研究两个 这种期望的领域：激光遵循CS+和 CS+产生的疼痛的预期。后者与避免未来痛苦有关，前者是 与逃避当前疼痛而不是方法有关，例如不遵守物理疗法，可以 引起一些疼痛。避免或逃避行为的增加与发生的情况有关，更糟 从骨关节炎到纤维肌痛的慢性疼痛综合征的结果。 我们建议通过直接从解剖学记录局部场电位（LFP）来研究这两个域 大脑中的成分涉及这两个领域，以期疼痛。我们的初步数据显示 LFP激活（ERPS事件相关电位＆ERS/ ERD-振荡能力的增加/降低） 杏仁核（艾米），海马形成和扣带回皮层的一部分，以响应未配对的CS+和 美国，可以介导调理并产生条件反应（CRS）。预期的CR包括 增加：自主活动（皮肤电导响应，SCR），以及在 CS+和我们，以及CS的不愉快和注意力（显着性）产生。的经验 与CS不同，我们很痛苦，与调节有关，但与CS不愉快或显着性无关，这是 与两个单独的域的存在一致。 CS SCR与ERS/ERD和ERC有关 频带和组件的功能与与CS+ US相关的频段和组件不同 相关的关联反过来与与CS不愉快和CS显着性有关的关联不同。模型 这些数据建议每个领域的网络，并得到研究的证据 解剖预测和fMRI信号。这两个模型共享包括艾米内部核的组成部分， 前后固定，但海马形成的组成部分不同 皮质，以及在一个结构内或相邻内部存在组件的存在所定义的本地网络中 结构。我们的前提是，这些模型中的组成部分将参与疼痛和调理过程， 并显示与两个域之一相关的激活作为单个组件或本地网络的一部分，以及 将显示为该域定义分布式层次网络的交互。 这项研究可能表明对药物开发以及手术或刺激疗法感兴趣的部位 疼痛综合征对疼痛的严重恐惧，例如对导致网络模型的神经活动的研究 基底神经节暗示了治疗靶标并改变了运动障碍的治疗。