Central Nervous System Amplification in Lumbar Failed Back Surgery Syndrome

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ABSTRACT Spine pain is the most common reason for which patients visit their doctor. Between 12-15% of the U.S. population seek care each year with associated costs exceeding $200 billion.1-3 Although the majority of pain patients can be managed with conservative therapy, there are millions of individuals who each year undergo surgery for an existing and refractory chronic pain condition, including surgeries such as lumbar spine surgery or joint arthroplasty.4-9 One of the most challenging sequelae for these patients is the failure to derive pain relief despite the surgical intervention. Lumbar failed back surgery syndrome (FBSS) is one of the most under- studied post-surgical pain syndromes and embraces a constellation of conditions describing recurrent or persistent low back pain, with or without leg pain, following one or more lumbar spine surgeries.10 Research has shown that there may be common characteristics at the individual level that contribute to poor analgesic outcomes after surgical procedures performed for the relief of pain.11-14 Individuals who fail to get meaningful relief of pain after surgery have been shown to share commonalities in how their central nervous systems (CNS) process and modulate nociceptive stimuli - known as CNS pain amplification or centralized pain - that can predispose them towards developing chronic pain after surgery. To date, there exists not even a single study investigating for the presence of CNS pain amplification in FBSS patients. Our overall hypothesis is that although peripheral nociceptive input is important in the initiation and maintenance of pain and symptom expression, patients who do not have a favorable analgesic outcome after lumbar spine surgery (FBSS) likely possess evidence of increased CNS pain amplification that contributes to the persistent expression of pain and co-morbid symptoms. The proposed novel initial studies are foundational and the necessary first steps to proving the presence of CNS pain amplification in this population, which will be the key driving force for a new avenue of research into this condition. The short-term goals of this K23 proposal are to use multiple rigorous research methods to establish that patients who fail to derive pain relief from lumbar spine surgery (FBSS) exhibit phenotypic and physiologic evidence of CNS amplification and centralized pain. Based on these findings, an R01 will be submitted to advance our long-term goal of designing and performing large-scale studies that will move us towards mechanisms-based “personalized analgesia” treatment strategies and risk stratification for lumbar spine surgery patients. The Candidate has shown a strong commitment to an academic career and has already performed impactful studies in the area of chronic pain. She has carefully selected multidisciplinary didactic and hands-on experiential training that will complement her existing knowledge and skill set. The proposed mentored career development award will enable her to acquire the skills necessary to perform both clinical trials and mechanistic studies in the perioperative setting and become a successful independent pain researcher.