Project Summary Statement of the Problem: Chronic post-surgical pain (CPSP), defined as pain lasting longer than two-months after surgery, is a significant public health problem affecting up to 80% of patients presenting for surgery. There are far-reaching consequences for quality of life and physical and emotional functioning for those affected by CPSP and complicating this crisis is the number of opioids prescribed after surgery with over 80% of patients receiving opioid prescriptions after low-risk surgery. Integrative research and effective treatment strategies are lacking. Overview of Research in the Laboratory: My grant funded research, including my current K23 Award, has focused on identifying biopsychosocial predictors of CPSP through the use of pre-clinical and clinical models and assuming a life-span perspective for identifying predictors and prevention of CPSP. In 2013, I published the largest prospective study to date identifying long-term pain trajectories and predictors of CPSP in young people and in 2018 results of Aim 1 of my K23 Award, utilizing an animal model of CPSP, received Editor’s Choice. My approach is to integrate clinical, psychological, and brain measures in order to understand the neurobiological processes that contribute to the evolution or resilience of CPSP. Goals for the Next 5 Years: In the next 5 years, I will continue to utilize a translational approach to examine risk factors for CPSP and extend upon my K23 work to: 1) utilize psychophysics and neuroimaging to understand the effects of CPSP on synaptic plasticity from adolescence into adulthood and 2) evaluate the effects of an evidence-based behavioral pain intervention, compared to Treatment as Usual, on the fNIRS signal in groups of adolescent and adult patients diagnosed with CPSP in order to compare Responders (improvement in pain severity, interference, & functioning) vs. Non-Responders. The projects outlined in the MIRA will be accomplished by my continued collaborations with colleagues who have expertise in surgery, pain psychophysics, neuroscience, and neuroimaging. Overall Vision of the Research Program: The goals of the R35 will be to: 1) enhance our understanding of the neurobiology of CPSP; 2) provide a metric to follow patients with CPSP in the clinic; 3) provide a metric for those who will chronify; 4) understand the age- related differences in CPSP; and 5) define an initial paradigm that may enhance our capability for developing individually tailored patient-oriented interventions at both a behavioral and pharmacological level.