PROJECT SUMMARY / ABSTRACT Chronic post-surgical pain (CPSP) is a major cause of new chronic pain, occurring between 10 - 40% after common surgical procedures. Thoracic surgery procedures have among the highest rates of chronic post- surgical pain (CPSP), with roughly 30 - 47% of patients developing new chronic pain within 6 months of surgery. While the high incidence of CPSP following thoracic surgery is well-described, the patient- and care- factors associated with the development of CPSP are still not clear. Some factors such as anxiety have been described; however, most cohorts lack the sample size to assess potentially important factors, including neuroimaging, quantitative sensory testing, and blood samples for genomics, metabolomics and proteomics. We believe that thoracic surgery is an ideal second surgical population to add to the Acute to Chronic Pain Signatures (A2CPS) program, complementing the first MCC population of knee arthroplasty, which has much lower rates of new CPSP but is a better cohort to identify risk factors for failure to resolve chronic pain. Our inter-disciplinary team from the proposed University of Michigan A2CP Multisite Clinical Center (MCC) has unparalleled expertise to examine the phenotypic and genotypic risk factors for the development of CPSP among patients undergoing thoracic surgery. Our PIs include an anesthesiologist, two surgeons, and a rheumatologist that have successfully collaborated in ongoing work, and partner within a statewide network of hospitals performing thoracotomy procedures, the Michigan Society of Thoracic and Cardiovascular Surgeons (MSTCVS) Quality Collaborative. Collaborative quality improvement programs including MSTCVS are funded by Blue Cross Blue Shield of Michigan to conduct participatory, provider-driven quality improvement initiatives, and our team has heavily leveraged these to study postoperative pain- and opioid-related outcomes and generate best practices. The implementation and dissemination of these best practices has dramatically reduced perioperative prescribing of opioids in the state of Michigan, and this strong partnership will enable us to recruit thoracotomy patients from a population-based sample across diverse healthcare systems. We will recruit 1800 patients from seven hospitals in Michigan undergoing surgery via a thoracic approach (lung resection, esophageal resection/reconstruction, and other general thoracic surgery). We joined the A2CPS Consortium in August 2020. Since that time, we have worked with the consortium to harmonize our protocols and prepare for our study launch. Through the multiple workgroups, we have determined that amendments to our protocols and procedures will be needed to harmonize with the MCC1. Moreover, given the progress made by the consortium in the more than year of work before we joined the consortium have made it such that we plan to launch our recruitment efforts in the second quarter of year one instead of the third quarter.

PROJECT NARRATIVE Chronic post-surgical pain after thoracic surgery is extremely common with current estimates between 30-47%. This multisite, prospective study will be the largest study ever conducted for chronic post-surgical pain and will probe patient factors not previously studied. Understanding the patient- and care-factors associated with the development of chronic pain after thoracic surgery would be applicable to other common surgical conditions and also enable clinical trials of high-risk individuals focused on prevention.