Contemporary Human Models of Postoperative Pain: A Biopsychosocial Investigation in General Surgery - Project Abstract Postoperative pain occurs in 80% of patients undergoing surgical procedures, with nearly 90% of these patients reporting moderate, severe or extreme pain1,2. Despite the attempts to understand and prevent severe pain after surgery, the percentage of patients who still suffer has remained unchanged for over 30 years4. For most patients, acute pain peaks between 24 and 48 hours after an operation6 and remits as the tissues heal, but for some patients, this unpleasant sensory and emotional experience can persist for months or even years7. Postoperative pain is complex and multifaceted, however, It has been suggested that if risk factors (biological and psychosocial) associated with chronic pain are recognized early in the preoperative period, then a patient is less likely to develop chronic postoperative pain (CPOP)5. Though preclinical pain models have provided evidence for some of the processes that might underlie the chronification of pain, postoperative pain in humans is complex and remains poorly understood10. General surgery provides a unique opportunity for researchers to examine the potential underpinnings of this transition (via human/clinical model) in a relatively controlled environment (I.e., operating room with procedures that are standard for specific operations). Thus, the proposed projects will employ the use of the biopsychosocial model, in the perioperative setting, to gain a deeper understanding of mechanisms that underlie nociception and the pain experience in humans. This will be achieved by examining aspects of endogenous pain modulation/ pain neurocircuitry (using quantitative sensory testing to assess diffuse noxious inhibitory control and pain facilitation), blood-based biomarkers (cytokines, chemokines, acute-phase reactants, pain-relative hormones, etc.) as well as relevant psychological features and social determinants of health (using standardized psychosocial and demographic assessments) in the preoperative setting that could potentially be used to predict which patients might experience more severe, frequent, and disabling pain in the postoperative setting and during other phases of recovery (follow-up). We will also examine biological markers in the immediate postoperative phase to assess immune response to surgical insult/injury. We anticipate that our work will ultimately identify novel biological and psychological correlates of postoperative pain that can be used to improve risk stratification and inform treatment decisions for patients who suffer from CPOP.