Grant: Discovery Grants Program - Individual

The purposes of this program of research are to: 1.Characterize and define the range of `normal' physiological and psychophysical responses to the VISION simulated trauma exposure 2.Predict the range of physiological and psychophysical responses following trauma 3.Explain the mechanisms of stress- and nociceptive- reactivity to trauma exposure. RATIONALE: A growing body of evidence supports stress system dysregulation as a key etiologic driver of the genesis of many chronic disease states including chronic pain and depression. Mouse models have led to robust stress simulation protocols and identifiable stress-reaction phenotypes such as `susceptible' or `resilient' through quantification of psychophysical markers. While we hypothesize similar phenotypes are present in humans, rigorous investigation requires a relevant, safe, and repeatable stress simulation protocol. To translate animal research to humans, we have created a first-of-its-kind research paradigm that pairs immersive virtual reality with proprioceptive sense of movement under controlled laboratory conditions allowing exploration of human reactions to trauma exposure from a simulated car crash that is under the mechanical threshold for tissue damage. RESEARCH PROGRAM: The goal of this program of research is to acquire new knowledge on the range of normal psychophysical reactions to motor vehicle collision (MVC), predict the magnitude of reaction based on person-level variables of sex, gender, age, and prior trauma, and test causal pathways of pain and distress development using advanced virtual reality integrated with proprioceptive robotic experience. Objectives 1 and 2 will be accomplished through observational designs with multilevel mixed models, while Objective 3 will be a factorial design exploring the specific parameters of MVC that have the greatest quantitative effect on physiological stress indicators in humans. Key physiological indicators across studies will be cardiovascular (heart rate, heart rate variability) and immune/inflammatory (blood cortisol, BDNF, TGFb1, IL-1b) with several secondary markers used to create robust `stress reactivity' phenotypes. These will be further explored for their associations with psychophysical indicators of change in state anxiety and nociceptive sensitivity (algometry) from pre to post trauma exposure. TRAINING: This program of research will support two high-quality trainee experiences at the PhD level who will be trained in a true transdisciplinary research environment through a strong collaborative network of basic, clinical, and social researchers. IMPACT: This work will further the field of stress and trauma research through new knowledge on `normal' reactions, identify who reacts most strongly, and what aspects of trauma are most distressing. Findings may be used to inform future ecological or clinical trials of stress-mitigating interventions intended to prevent the genesis of post-traumatic chronic disease states.