Prediction and Prevention of Persistent Post-Mastectomy Pain

描述（由申请人提供）：慢性疼痛对个人和社会都是毁灭性的。在老龄化人口中，手术是慢性疼痛的一个日益增加的原因，术后持续疼痛的比例在10-65%之间。特别是，持续的乳房切除术后疼痛（PPMP）发生在大约三分之一的乳房切除术后妇女身上。PPMP的发生似乎与手术、化疗和放射治疗的类型没有很大的关系，这表明个体特异性因素可能起着更重要的作用。事实上，候选人最近的研究表明，疼痛敏感性（心理物理学）的个体差异与PPMP的关系比手术/医学变量更密切。具体来说，感官测试显示，患有PPMP的女性比没有患这种慢性疼痛的女性有更低的压力疼痛阈值和更大的疼痛刺激时间总和。此外，焦虑、抑郁、灾难化和躯体化等社会心理因素在PPMP女性中更为突出。这些初步的回顾性研究表明，个体心理生理和社会心理特征可能是PPMP的重要危险因素。因此，本研究的第一个目的是对乳房切除术妇女进行全面、前瞻性的研究，以确定术前心理生理和社会心理因素与PPMP发生的关系。第二个目的是利用目的1中收集的数据建立PPMP的预测模型，从而允许术前计算任何面临乳房切除术的患者的“PPMP风险评分”。然后将在另一组患者中进行验证（研究2）。该风险评分将用于充实一项具有较大比例PPMP高风险妇女的干预性试验，目的3是调查这种充实是否能比未筛选组更有效和敏感地确定预防药物的效果。这些研究将为仅在需要它们的高风险患者中有效地测试新型药物奠定基础。在这个应用程序的候选人，Dr. Kristin Schreiber是一个博士训练有素的神经科学家和麻醉师在一个领先的学术，高容量的乳腺癌中心。拟议的研究将使医疗保健提供者了解导致术后慢性疼痛的潜在机制，从而对术后持续疼痛的高风险患者进行更有针对性的预防性治疗。她的职业发展导师是外科、医学、心理、术前评估、临床前建模和生物统计学方面的专家。候选人具有强大的科学背景，在一个具有强大临床试验传统和基础设施的中心接受高级统计学方面的正式培训和多样化的指导，将确保她成功实现预防PPMP的科学和职业目标，并为预防其他持续性术后疼痛综合征奠定基础。

DESCRIPTION (provided by applicant): Chronic pain is devastating both to individuals and society. In an aging population, surgery is an increasing cause of chronic pain, with rates of persistent post-operative pain ranging from 10-65%. In particular, Persistent Post-Mastectomy Pain (PPMP) occurs in roughly one third of women who have had mastectomy. The occurrence of PPMP does not seem to be strongly determined by the type of surgery, chemotherapy, and radiation treatment, suggesting that individual person-specific factors may play a more important role. In fact, recent studies by the candidate indicate that individual differences in pain sensitiity (psychophysics) are more closely associated with PPMP than surgical/medical variables. Specifically, sensory testing revealed that women who developed PPMP had lower pressure pain thresholds and greater temporal summation of pain stimuli than women who did not develop this chronic pain condition. Moreover, psychosocial factors such as anxiety, depression, catastrophizing, and somatization were more prominent in women with PPMP. These preliminary, retrospective studies suggest that individual psychophysical and psychosocial characteristics could be important risk factors for PPMP. Accordingly, the first Aim of this study is to comprehensively and prospectively study women having mastectomy surgery, to determine the relationship between pre-operative psychophysical and psychosocial factors and the development of PPMP. The second Aim is to develop a prediction model for PPMP using the data collected in Aim 1, thus allowing a preoperative calculation of a "PPMP risk score" for any patient facing mastectomy. This will then be validated in a separate group of patients (study 2). Study will be this risk score will be used to enrich an interventional trial with a greater proporton of women at high risk of PPMP, with Aim 3 to investigate whether this enrichment allows more efficient and sensitive determination of a preventative drug's effect than in an unscreened group. These studies will lay the groundwork to efficiently test novel pharmaceutics only in the high risk patients who need them. The candidate in this application, Dr. Kristin Schreiber is a PhD-trained Neuroscientist and Anesthesiologist at a leading academic, high-volume breast cancer center. The proposed studies would inform healthcare providers about the underlying mechanisms contributing to chronic pain after surgery, thus allowing more targeted, preventive treatment in patients who are high risk for persisting post-operative pain. Her career development mentors are experts in surgical, medical, psychological, and preoperative assessment, preclinical modeling, and biostatistics. The candidate's strong scientific background, taken together with the proposed formal training in advanced statistics and diverse mentorship, in a center that has a strong tradition and infrastructure for clinical trials, will enure the successful achievement of her scientific and career objectives to prevent PPMP and lay the groundwork for prevention of other persistent post-surgical pain syndromes.