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

描述(由申请人提供)： 创伤后应激障碍(PTSD)与战斗相关的疼痛的生物行为机制在理解上存在着根本性的差距。虽然大量文献表明，患有创伤后应激障碍的个体经历了更强的疼痛敏感性，但也有其他文献表明，患有创伤后应激障碍的个体表现出疼痛止痛。通过解决这一争议并填补我们认识上的空白，我们可以在战斗相关的创伤后应激障碍中识别疼痛的生物标记。这项谅解将有一个长期目标，即允许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。本应用程序的目标是 目的是通过将患有创伤后应激障碍的退伍军人的主观自我报告和客观大脑反应与实验性疼痛联系起来，全面了解与战斗相关的创伤后应激障碍的疼痛。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的退伍军人相比，患有创伤后应激障碍的退伍军人将对疼痛表现出复杂的反应，这既表现出最初的超敏反应，即由觉醒调节的大脑对疼痛的主观和客观反应增加，也表明随后的疼痛止痛，即通过回避调节的对反复疼痛的主观和客观大脑反应减弱。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，一旦了解了创伤后应激障碍对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，这是患有战斗相关创伤后应激障碍的退伍军人所独有的。在强大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)表征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)确定在首次应用实验性热疼痛后，患有当前创伤后应激障碍的退伍军人对疼痛处理的神经基础；3)确定在目前患有创伤后应激障碍的退伍军人中反复应用实验性热疼痛的主观和神经变化的神经基础；以及4)确定患有慢性疼痛的退伍军人对疼痛处理的神经基础。这种方法是创新的，因为它：1)检查主观和大脑对首次和重复应用实验性疼痛的反应，并将这些反应与创伤后应激障碍的症状和与疼痛相关的认知和行为(如回避)联系起来；2)使用四组模型(创伤后应激障碍、没有创伤后应激障碍的慢性疼痛、创伤暴露对照和非创伤对照)，这对于识别创伤相关、创伤后应激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)只检查与战斗相关的创伤，从而增加了检测战斗应激具体影响疼痛处理的程度的能力，并且对退伍军人具有更广泛的概括性和对退伍军人护理的影响。这项研究具有重要意义，因为它提供了一个生物学模型和一组神经标记物，可以解释创伤后应激障碍的功能性疼痛敏感性，提供对加剧疼痛和创伤后应激障碍症状的机制的洞察，以及这些机制与没有创伤后应激障碍的疼痛有何不同。

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.