Central Nervous System Amplification in Lumbar Failed Back Surgery Syndrome

摘要 脊椎疼痛是患者就诊的最常见原因。占美国人口的12%-15%。 人口每年寻求护理的相关费用超过2,000亿美元1-3，尽管大多数人感到痛苦 患者可以通过保守治疗来管理，每年有数百万人接受 对现有的顽固性慢性疼痛进行手术，包括腰椎手术等手术 或关节成形术。对这些患者来说，最具挑战性的后遗症之一是无法产生疼痛 尽管进行了手术干预，病情还是缓解了。腰椎手术失败综合征(FBSS)是最常见的腰椎手术失败综合征之一。 研究了手术后疼痛综合征，并包含了一系列描述复发或 在一次或多次腰椎手术后，持续性下腰痛，伴或不伴腿痛。 研究表明，在个体层面上可能存在共同的特征，这些特征有助于 手术止痛后止痛效果不佳。11-14名患者 手术后获得有意义的疼痛缓解已被证明有共同点在他们的中枢 神经系统(CNS)处理和调制伤害性刺激--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出现慢性疼痛。到目前为止，有 目前甚至没有一项研究调查FBSS患者中是否存在中枢神经系统疼痛放大。我们的 总体假设是，尽管外周伤害性输入在启动和维持过程中很重要 疼痛和症状表现，腰椎术后止痛效果不佳的患者 手术(FBSS)可能有证据表明中枢神经系统疼痛放大增加，这有助于持续性 表现出疼痛和共病症状。拟议的新的初步研究是基础性的， 证明这一人群中存在中枢神经系统疼痛放大的必要的第一步，这将是关键 为研究这种情况开辟一条新途径的动力。这项K23提案的短期目标是 使用多种严格的研究方法来确定无法从腰椎获得疼痛缓解的患者 脊柱外科(FBSS)表现为中枢神经系统扩大和集中性疼痛的表型和生理学证据。 根据这些调查结果，将提交R01，以推进我们设计和执行的长期目标 将推动我们转向基于机制的“个性化止痛”治疗策略的大规模研究 以及腰椎手术患者的风险分层。 候选人表现出对学术事业的强烈承诺，并已经表现出色 在慢性疼痛领域的有影响力的研究。她精心选择了多学科的授课和实践 体验式培训将补充她现有的知识和技能。建议的被指导职业 发展奖将使她获得必要的技能，进行临床试验和 在围手术期环境中进行机制研究，并成为一名成功的独立疼痛研究人员。

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.