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，他致力于一项研究 在南非的职业生涯，与领先的跨学科研究的职业愿景，以了解疼痛机制， nisms和开发可扩展的，有针对性的治疗，安全，有效地缓解疼痛，在资源有限的 设置.通过5年的专注研究时间，她将能够实现她系统的职业发展， 她计划（1）加深对研究项目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） 获得宝贵的第一手经验，在南非进行以社区为基础的研究。这将使- 她是第一位南非跨学科专家，研究心理学、免疫学和心理学之间的相互作用。 艾滋病的病理和疼痛职业发展计划是围绕协调的、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;在南非进行实践研究 非洲，并从一个精心挑选的经验丰富的研究科学家团队密切指导。 研究艾滋病毒感染者经常伴随着持续的疼痛和心理社会困扰（PSD）。 大多数HIV相关的疼痛不能用周围神经病变来解释，但类似于复杂的慢性疼痛条件。 其中免疫系统已被发现对刺激有夸大的反应（炎症， 炎症反应性）。已知PSD有助于免疫失调和疼痛。一种途径， PSD可能通过炎症反应（IR）影响HIV相关疼痛-但这尚未确定。在 本研究项目，第1阶段（具体目标1）旨在表征PSD，IR， 中枢致敏和持续疼痛。它将使用一项队列研究，基线测量来自HIV+ 有/无持续性疼痛的人（2组），以及来自 每一组在6个月的时间里。调解分析将澄清IR是否代表了 PSD对HIV相关疼痛的影响;组间比较将对比 伴有和不伴有持续性疼痛的患者;广义混合效应模型将检查PSD、IR 和疼痛的变化。这将是第一次描述心理和心理之间的联系。 社会压力、炎症反应、中枢敏感和HIV相关疼痛。第2阶段（具体目标2） 旨在制定和确定一个务实的，可扩展的，以应对为重点的 在南非采取干预措施，减少艾滋病毒感染者的痛苦和痛苦。干预措施将得到发展- 在文化安全、逐步形成的过程中，包括社区， 和接收器接合。一项小型开放性初探性试验（n = 10），纳入了干预措施的迭代修订 内容和交付将用于测试干预的可行性和可接受性，并解决问题的简单， 为未来的充分有效的临床试验提供信息的心理和评估程序。

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.