Personalizing Perioperative Preventive Analgesia: Translational Studies Investigating the Biopsychosocial Underpinnings of Enhanced Pain Propensity

项目总结

PROJECT SUMMARY Over 230 million people undergo surgery annually. The experience of postsurgical pain varies among individuals, but a significant proportion (20-30%) of patients experience surgical site pain lasting at least a year postoperatively. Such Persistent Post-Surgical Pain (PPSP) causes physical and mental suffering and disability and lengthens exposure to opioid analgesics, potentially placing patients at risk of addiction. Despite excellent research in basic research indicating potential mechanisms involved in the transition of acute to chronic pain, little success at translating these findings to actual prevention of persistent postoperative pain in human patients has been realized. My research program has developed a working human model of this transition, by systematic and longitudinal studying pain before, during and after a variety of surgeries. We have identified several patient-level risk factors that predict who is high-risk for developing PPSP, allowing more efficient study of this problem, as well as insight into relevant mechanisms, in humans. A crucially important factor in determining the trajectory of PPSP appears to be the tendency for the pain signal to be amplified. While pain amplification may be protective in the short term, it becomes dysfunctional if excessive or persistent. In our psychophysics lab, we study measures that indicate excessive amplification response of the nervous system in some individuals in response to standardized pain testing. We also measure psychosocial factors such as stress, sleep disruption, and catastrophizing (a mental process by which rumination, magnification, and worry increase salience and importance), which can also amplify the pain signal. Importantly, pain amplification is more prominent in some individuals, and accounts for a sizeable amount of the variation in pain resulting from surgery (and far more than the surgical extent). We have developed a system to easily and non-invasively test this “amplification phenotype” in individuals BEFORE surgery, using modified bedside quantitative sensory tests, and brief, validated psychosocial questionnaires. My research program has optimized measurement of our patients’ preoperative amplification phenotype, to help target both known and novel non-opioid preventive treatments to these high-risk individuals. Our goals for the next 5 years of this R35 award are: (1) to efficiently target the prevention of persistent pain and opioid use after surgery in high-risk individuals, (2) to understand and target the underlying mechanisms contributing to the development of PPSP, including understanding how pain amplification relates to the inflammatory response to surgery, (3) to more widely apply preventive strategies, understanding their differential efficacy among diverse samples of patients. As an Anesthesiologist with formal training in pain neuroscience, psychophysical and psychosocial assessments, and practical experience in conducting translational studies, I am well-situated to conduct such well-designed mechanistic studies.