Neurobehavioral Correlates of Pain in Post-Traumatic Stress Disorder (PTSD)

创伤后应激障碍 (PTSD) 中疼痛的神经行为相关性

• 批准号: 8958793
• 负责人: Irina A Strigo
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8958793
• 关键词: Absence of pain sensation; Address; Affect; Affective; Amygdaloid structure; Arousal; Attenuated; Behavior; Behavioral; Biological Markers; Biological Models; Brain; Caring; Characteristics; Clinical; Cognition; Cognitive; Complex; Data; Emotional; Exposure to; Goals; Health; Heating; Hypersensitivity; Individual; Insula of Reil; Intervention Trial; Knowledge; Laboratories; Light; Link; Literature; Mediating; Modeling; Neurobiology; Outcome; Pain; Patient Self-Report; Personal Satisfaction; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Reporting; Research; Risk; Self-Injurious Behavior; Sensory; Stress; Symptoms; Testing; Therapeutic Intervention; Time; Trauma; Veterans; anxiety sensitivity; attenuation; base; biobehavior; chronic pain; clinical care; combat; cost; experience; improved; innovation; insight; neurobehavioral; prescription opiate; public health relevance; relating to nervous system; response

DESCRIPTION (provided by applicant): There is a fundamental gap in understanding the biobehavioral mechanism of pain in Post Traumatic Stress Disorder (PTSD) related to combat. While a large body of literature suggests that individuals with PTSD experience increased pain sensitivity, others have shown that individuals with PTSD display pain analgesia. By addressing this controversy and filling this gap in our understanding, we can identify biological markers of pain in combat-related PTSD. This understanding will have the long-term goal of allowing for developing scientifically based therapeutic intervention trials for Veterans suffering from PTSD. The objective of this application is to gain a comprehensive understanding of pain in combat-related PTSD by relating subjective self- report and objective brain responses to experimental pain in Veterans with PTSD. Our central hypothesis is that Veterans with PTSD compared to both Veterans with chronic pain and traumatized Veterans without PTSD, will show complex response to pain demonstrating both, initial hypersensitivity, i.e., increased subjective and objective brain responses to pain that wil be mediated by arousal, as well as subsequent pain analgesia, i.e., attenuated subjective and objective brain response to repeated pain that will be mediated by avoidance. This hypothesis was formulated on the basis of preliminary data produced in the applicant's laboratory. The rationale is that once the dynamic brain response to experimental pain in PTSD is understood, we can build a comprehensive, neurally-based model of pain sensitivity that is unique to Veterans with combat-related PTSD. Guided by strong preliminary data this central hypothesis will be tested by pursuing four specific aims: 1) To characterize sensory and emotional responses to pain in Veterans with current PTSD; 2) To identify the neural substrates of pain processing in Veterans with current PTSD following the initial application of experimental heat pain; 3) To determine which neural substrates underlie subjective and neural changes to repeated application of experimental heat pain in Veterans with current PTSD; and 4) To determine the neural substrates of pain processing in Veterans with chronic pain. This approach is innovative because it: 1) examines subjective and brain responses to initial and repeated application of experimental pain, and links these responses to symptoms of PTSD and pain-related cognitions and behaviors(e.g., avoidance); 2) uses a four group model(PTSD, chronic pain no PTSD, trauma exposed controls, and non-traumatized controls), which is necessary to identify trauma-related, PTSD-related and chronic pain-related subjective and brain responses to pain, and 3) examines only combat-related trauma, thereby increasing power of detecting the degree to which combat stress specifically affects pain processing and has more generalizability to Veterans and implications for Veteran care. This research is significant because it provides a biological model and a set of neural markers that could explain dysfunctional pain sensitivity in PTSD, provide insight into the mechanisms that exacerbate pain and PTSD symptoms, and how these mechanisms differ from pain without PTSD.

描述（由申请人提供）： 在理解与战斗有关的创伤后应激障碍（PTSD）疼痛的生物行为机制方面存在根本性的差距。虽然大量文献表明PTSD患者的疼痛敏感性增加，但其他文献表明PTSD患者显示疼痛镇痛。通过解决这一争议并填补我们理解中的这一空白，我们可以确定与战斗相关的PTSD疼痛的生物标志物。这种理解将有一个长期的目标，即为患有创伤后应激障碍的退伍军人开发基于科学的治疗干预试验。本申请的目的 通过对创伤后应激障碍退伍军人的主观自我报告和客观脑反应与实验性疼痛的联系，获得对创伤后应激障碍疼痛的全面理解。我们的中心假设是，与患有慢性疼痛的退伍军人和没有创伤后应激障碍的创伤退伍军人相比，患有创伤后应激障碍的退伍军人将显示出对疼痛的复杂反应，表明初始超敏反应，即，增加的主观和客观脑对将由唤醒介导的疼痛的反应，以及随后的疼痛镇痛，即，减弱主观和客观大脑对重复疼痛的反应，这将通过回避来介导。这一假设是根据申请人实验室提供的初步数据提出的。其基本原理是，一旦了解了PTSD中实验性疼痛的动态大脑反应，我们就可以建立一个全面的，基于神经的疼痛敏感性模型，这是退伍军人与战斗相关的PTSD所独有的。在强有力的初步数据的指导下，这一中心假设将通过追求四个具体目标来检验：1）描述患有当前创伤后应激障碍的退伍军人对疼痛的感觉和情感反应; 2）在最初应用实验性热痛后，确定患有当前创伤后应激障碍的退伍军人疼痛处理的神经基质; 3）确定哪些神经基质是当前患有PTSD的退伍军人重复应用实验性热痛的主观和神经变化的基础;（4）确定退伍军人慢性疼痛患者疼痛加工的神经基质。这种方法是创新的，因为它：1）检查主观和大脑对实验疼痛的初始和重复应用的反应，并将这些反应与PTSD的症状和疼痛相关的认知和行为（例如，回避）;（2）采用四组模型（PTSD、慢性疼痛无PTSD、创伤暴露对照和非创伤对照），这对于识别创伤相关、PTSD相关和慢性疼痛相关的主观和大脑对疼痛的反应是必要的，以及3）仅检查战斗相关的创伤，从而增加了检测战斗压力具体影响疼痛处理的程度的能力，并且对退伍军人具有更大的普遍性，对退伍军人护理的影响。这项研究意义重大，因为它提供了一个生物学模型和一组神经标志物，可以解释PTSD中功能失调的疼痛敏感性，提供了对加剧疼痛和PTSD症状的机制的深入了解，以及这些机制与没有PTSD的疼痛有何不同。