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.
Pain worsens well-being and functioning contributing significantly to poorer health outcomes in Veterans suffering from Posttraumatic stress disorder(PTSD). The proposed research is relevant to the Veterans' health since it will provide mechanistic understanding of pain processing in Veterans with PTSD and show that PTSD uniquely contributes to aberrant pain response above and beyond that associated with trauma and/or chronic pain. This will provide neurobiological evidence for theorized conceptual models of the co-occurrence of pain and PTSD in the Veteran population and, potentially, shed light on how those treatments that are currently effective for PTSD (e.g., Prolonged Exposure) may be applied to Veterans whose PTSD symptoms are aggravated by pain. This application will advance our knowledge of the neurobiological basis of PTSD, which is an important first step in improving the clinical care of Veterans with PTSD.
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