Psychosocial distress, inflammatory reactivity and central sensitization in the pathway to HIV-related pain: characterizing the associations and developing a pragmatic, coping-focused intervention.

项目摘要 候选人马登博士是开普敦大学的高级讲师，致力于一项研究 在南非的职业生涯，职业愿景是领导跨学科研究以了解疼痛机制- 并开发可扩展、有重点的治疗方法，安全有效地缓解资源有限的患者的疼痛 设置。有了5年的专注研究时间，她将能够实现她系统的职业发展- 发展计划：(1)加深对研究计划中先进方法和专业知识的理解 管理，(2)扩大她对艾滋病毒、免疫学和心理社会对疼痛的影响的知识，以及(3) 在南非开展基于社区的研究方面获得宝贵的第一手经验。这将会使- 让她成为南非第一位研究心理学、免疫和医学之间互动的跨学科专家 艾滋病病毒的病原学和疼痛。职业发展计划是围绕协调、跨学科的培训而制定的 在开普敦大学、哈佛大学和密歇根大学；在南方实践研究 非洲，以及精心挑选的经验丰富的研究科学家团队的密切指导。 艾滋病毒携带者的研究经常伴随着持续性疼痛和心理社会痛苦(PSD)。 大多数HIV相关疼痛不是由周围神经病变解释的，而是类似于复杂的慢性疼痛条件- 免疫系统被发现对刺激有夸大反应的疾病(炎症- 交配反应性)。众所周知，PSD会导致免疫失调和疼痛。一条途径，通过它 PSD可能通过炎症反应(IR)影响HIV相关疼痛--但这一点尚未确定。在……里面 本研究项目第一阶段(具体目标1)旨在描述PSD、IR、 艾滋病毒的中枢敏感化和持续性疼痛。它将使用一项队列研究，其中包括艾滋病毒的基线测量 有/没有持续性疼痛的人(2组)，并对来自以下方面的部分参与者进行纵向跟踪 每组为期6个月。中介分析将澄清IR是否代表了 PSD对HIV相关疼痛的影响；小组比较将比较IR和中枢敏化在 那些有和没有持续性疼痛的人；广义混合效应模型将检查PSD、IR的波动 随着时间的推移，每组患者的疼痛程度。这将是第一次描述精神病患者之间的联系。 社交痛苦、炎症反应、中枢敏感化和艾滋病毒相关疼痛。阶段2(具体目标2) 旨在开发和确定务实的、可扩展的、以应对为重点的 减少南非艾滋病毒携带者痛苦和痛苦的干预。干预将是发展的- OpEd，用于非专业人员的交付，在包括社区在内的文化安全的逐步形成过程中 和接收器接洽。一项包含反复修订干预的小型开放试验试验(n=10) 内容和交付将用于测试干预的可行性和可接受性，并对实施情况进行故障排除- 沉着状态和评估程序，为未来的全能临床测试提供信息。

Project Summary Candidate Dr Madden is a senior lecturer at the University of Cape Town who is committed to a research career in South Africa, with the career vision of leading interdisciplinary research to understand pain mecha- nisms and develop scale-able, focused treatments that safely and effectively relieve pain in resource-limited settings. With 5 years of dedicated research time, she will be able to implement her systematic career devel- opment plan to (1) deepen her understanding of advanced methodology and expertise in research program management, (2) expand her knowledge of HIV, immunology and psychosocial influences on pain, and (3) gain valuable first-hand experience in conducting community-based research in South Africa. This will de- velop her as the first South African cross-disciplinary expert in the interactions between psychology, immu- nology and pain in HIV. The career development plan is built around coordinated, cross-disciplinary training at the University of Cape Town, Harvard University and University of Michigan; hands-on research in South Africa, and close mentorship from a carefully selected team of highly experienced research scientists. Research Living with HIV is frequently accompanied by persistent pain and psychosocial distress (PSD). Most HIV-related pain is not explained by peripheral neuropathy, but resembles complex chronic pain condi- tions in which the immune system has been found to have an exaggerated response to provocation (inflam- matory reactivity). PSD is known to contribute to immune dysregulation and to pain. One pathway by which PSD may influence HIV-related pain is via inflammatory reactivity (IR) – but this has not been established. In this Research Project, Phase 1 (Specific Aim 1) aims to characterize the relationships between PSD, IR, central sensitization and persistent pain in HIV. It will use a cohort study with baseline measures from HIV+ people with/without persistent pain (2 groups), and longitudinal follow-up of a subsample of participants from each group over a 6-month period. Mediation analysis will clarify whether IR represents a pathway for the influence of PSD on HIV-related pain; group comparisons will contrast IR and central sensitization between those with and without persistent pain; generalized mixed effect models will examine fluctuations in PSD, IR and pain over time in each group. This will be the first characterization of the associations between psycho- social distress, inflammatory reactivity, central sensitization and HIV-related pain. Phase 2 (Specific Aim 2) aims to develop and determine the feasibility and acceptability of a pragmatic, scale-able, coping-focused intervention to decrease distress and pain in people with HIV in South Africa. The intervention will be devel- oped, for non-specialist delivery, during a culturally secure, stepwise formative process including community and receiver engagement. A small open pilot trial (n = 10) that incorporates iterative revision of intervention content and delivery will be used to test intervention feasibility and acceptability and to troubleshoot imple- mentation and assessment procedures to inform future, fully powered clinical testing.