Persistent Post-Mastectomy Pain: Randomized Clinical Trial of Targeted Pain Coping Skills Training (Targeted-PCST) with Mediational Analysis

摘要 乳腺癌手术后持续疼痛越来越被认为是一个重要的临床和公众问题。 健康问题，由于大量的妇女受到影响，强大的负面影响，持续的疼痛有 情绪和身体功能及其经济成本。超过25万人中的大部分 今年，美国新诊断出乳腺癌的妇女将接受手术，作为治疗的一部分。 治疗手术切除受影响乳房（乳房切除术）后持续疼痛的患病率， 更有限的手术（乳房肿瘤切除术）比例较高，在所有研究中为25-60%。与急性术后不同， 疼痛是对手术创伤的正常反应，手术部位或附近的持续疼痛具有 不确定的多方面病因，没有令人满意的药物治疗。一个关键问题是， 关键的疼痛相关心理社会因素是持续性疼痛的持续负担的驱动因素， 可以通过非药物干预来改善。该奖项计划的研究将提供 对乳腺癌后持续性疼痛中疼痛灾难化的假设驱动作用的第一个关键测试 手术它还将探讨其他两个可能导致负担的关键心理社会变量的作用 与乳腺癌手术后持续疼痛相关：从事有价值活动的自我效能， 心理承受能力。我们已经开发，手册化，并试点测试疼痛应对技能培训 专门针对乳腺癌手术后持续疼痛妇女需求的干预措施 （有针对性的PCST），旨在减少痛苦灾难化，提高自我效能， 活动，降低心理承受能力。我们提出了一个多中心，随机临床试验， 评估靶向PCST干预的有效性。该研究将在9个不同的肿瘤学中进行 诊所：5家附属于杜克大学/杜克癌症网络，4家附属于杜克大学 匹兹堡/UPMC希尔曼癌症中心。受试者（N=564）将随机接受：1） 靶向PCST，2）一般健康教育干预（对照），或3）常规护理（对照）。参与者将 干预前和3个月（干预后）、6个月随访和12个月时的完整评估 个月随访。研究目的：目的1：检查靶向PCST对术后持续性 疼痛严重性和干扰（即，PEG评分）、情绪困扰（焦虑和抑郁）和癌症- 具体的苦恼。目的2：研究靶向PCST对疼痛灾难化、疼痛自我效能的影响， 和心理承受能力，并评估这些变量作为有针对性的益处的可能中介， PCST。目的3：评价靶向PCST对疼痛敏感性和中枢致敏性的影响，并探讨 这些变量的变化是否介导了疼痛严重程度和干扰的组间差异。

Abstract Persistent pain following breast cancer surgery is increasingly recognized as an important clinical and public health issue due to the large number of women affected, the powerful negative impact that persistent pain has on emotional and physical functioning and its financial costs. Most of the more than a quarter of a million women newly diagnosed with breast cancer in the U.S. this year will undergo surgery as a part of curative treatment. The prevalence of persistent pain following surgical removal of the affected breast (mastectomy) or more limited surgeries (lumpectomy) is high, ranging from 25-60% across studies. Unlike acute post-operative pain, which is a normal response to surgical trauma, persistent pain at or near the surgical site has an uncertain multifaceted etiology, and no satisfactory pharmacological treatment. A critical question is whether key pain-related psychosocial factors are drivers of the continuing burden of persistent pain, and whether they could be ameliorated by non-pharmacological intervention. The research planned under this award will provide a first critical test of the hypothesized driving role of pain catastrophizing in persistent pain after breast cancer surgery. It also will explore the role of two other key psychosocial variables that may contribute to the burden associated with persistent pain after breast cancer surgery: self-efficacy for engaging in valued activities and psychological inflexibility. We have developed, manualized, and pilot tested a pain coping skills training intervention that specifically targets the needs of women with persistent pain following breast cancer surgery (Targeted PCST) and aims to reduce pain catastrophizing, increase self-efficacy for engaging in valued activities, and decrease psychological inflexibility. We propose a multiple-site, randomized clinical trial to evaluate the efficacy of the Targeted-PCST intervention. The study will be conducted in 9 diverse oncology clinics: 5 affiliated with Duke University/Duke Cancer Network and 4 affiliated with the University of Pittsburgh/UPMC Hillman Cancer Center. Participants (N=564) will be randomized to either receive: 1) Targeted-PCST, 2) a general health education intervention (control), or 3) usual care (control). Participants will complete assessments pre-intervention and at 3 months (post-intervention), 6 months follow-up, and 12 months follow-up. Study aims are: Aim1: Examine the impact of Targeted-PCST on persistent post-surgical pain severity and interference (i.e., PEG score), emotional distress (anxiety and depression), and cancer- specific distress. Aim 2: Investigate the impact of Targeted-PCST on pain catastrophizing, pain self-efficacy, and psychological inflexibility, and evaluate these variables as possible mediators of the benefits of Targeted- PCST. Aim 3: Evaluate the impact of Targeted-PCST on pain sensitivity and central sensitization, and explore whether changes in these variables mediate group differences in pain severity and interference.