Central Nervous System Amplification in Lumbar Failed Back Surgery Syndrome

摘要 脊柱疼痛是患者就诊的最常见原因。12-15%的美国 每年有超过2000亿美元的人口寻求护理，相关费用超过2000亿美元。 患者可以通过保守治疗进行管理，每年有数百万人接受 针对现有和难治性慢性疼痛状况的手术，包括腰椎手术等手术 或关节成形术。4 -9这些患者最具挑战性的后遗症之一是无法产生疼痛 尽管有手术干预，腰椎手术失败综合征（FBSS）是一种最常见的腰椎手术失败综合征。 研究了术后疼痛综合征，包括一系列描述复发或 在一次或多次腰椎手术后出现持续性腰痛，伴或不伴腿部疼痛。 研究表明，在个人层面上可能存在共同的特征， 为缓解疼痛而进行的外科手术后镇痛效果差。11 -14 手术后疼痛得到有意义的缓解，已经表明，在他们的中心如何共享的共性， 神经系统（CNS）处理和调节伤害性刺激-称为CNS疼痛放大或 集中性疼痛-这可能使他们在手术后容易发展为慢性疼痛。迄今为止 甚至没有一项研究调查FBSS患者中CNS疼痛放大的存在。我们 总的假设是，虽然外周伤害性输入是重要的启动和维持 疼痛和症状表达，腰椎术后镇痛效果不佳的患者 手术（FBSS）可能具有增加CNS疼痛放大的证据， 疼痛和共病症状的表现。提出的新的初步研究是基础性的， 必要的第一步，以证明存在中枢神经系统疼痛放大在这一人群中，这将是关键 这是一种新的研究途径的推动力。K23提案的短期目标是 使用多种严格的研究方法，以确定腰椎疼痛缓解失败的患者 脊柱手术（FBSS）表现出CNS放大和集中性疼痛表型和生理学证据。 根据这些发现，将提交R 01，以推进我们设计和执行的长期目标 大规模的研究将使我们转向基于机制的“个性化镇痛”治疗策略 和腰椎手术患者的风险分层。 候选人已表现出对学术生涯的坚定承诺，并已履行 在慢性疼痛领域的影响力研究。她精心挑选了多学科的教学和动手 体验式培训，将补充她现有的知识和技能。建议的指导职业 发展奖将使她获得必要的技能，进行临床试验， 在围手术期的机制研究，并成为一个成功的独立的疼痛研究。

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.