Prediction and Prevention of Persistent Post-Mastectomy Pain

描述(申请人提供)：慢性疼痛对个人和社会都是毁灭性的。在老龄化的人口中，手术是慢性疼痛的一个日益增加的原因，手术后持续性疼痛的比率从10%到65%不等。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接受过乳房切除术的女性身上。PPMP的发生似乎不受手术、化疗和放射治疗类型的强烈影响，这表明个人特有的因素可能起到更重要的作用。事实上，候选人最近的研究表明，疼痛敏感度(心理物理学)的个体差异与PPMP的关系比外科/医学变量更密切。具体地说，感觉测试显示，与没有出现这种慢性疼痛状况的女性相比，患有PPMP的女性压力痛阈值更低，疼痛刺激的时间总和更大。此外，在患有PPMP的女性中，焦虑、抑郁、灾难和躯体化等心理社会因素更为突出。这些初步的回溯性研究表明，个体的心理物理和心理社会特征可能是PPMP的重要危险因素。因此，本研究的第一个目的是全面和前瞻性地研究女性乳房切除手术，以确定术前心理物理和心理社会因素与PPMP发生的关系。第二个目标是利用目标1中收集的数据开发PPMP预测模型，从而允许在手术前计算任何面临乳房切除的患者的PPMP风险评分。然后将在一组单独的患者中进行验证(研究2)。研究将利用这一风险评分来丰富一项干预性试验，使其具有更大比例的PPMP高危女性，目标3调查这种强化是否比未筛查的组更有效和更灵敏地确定预防药物的效果。这些研究将为仅在需要的高危患者中有效测试新药物奠定基础。这份申请的候选人Kristin Schreiber博士是一名受过博士培训的神经学家和麻醉师，供职于一家领先的学术规模大的乳腺癌中心。拟议的研究将向医疗保健提供者通报手术后慢性疼痛的潜在机制，从而允许对手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、心理学和术前评估、临床前建模和生物统计学方面的专家。候选人强大的科学背景，再加上拟议的高级统计学正式培训和多样化的指导，在一个拥有强大的临床试验传统和基础设施的中心，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手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.