HL-Phenotypic Characterization of Chronic Pain in Adults with Sickle Cell Disease

镰状细胞病成人慢性疼痛的 HL 表型特征

• 批准号: 8786653
• 负责人: ROBERT E MOLOKIE
• 金额: $ 77.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8786653
• 关键词: Address; Adult; Affective; African; African American; Age; American; Animals; Area; C Fiber; Caring; Characteristics; Chronic; Data; Descriptor; Dose; Environmental Risk Factor; Environmental Wind; Epigenetic Process; Esthesia; Etiology; Fiber; Filament; Future; Gender; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Goals; Heating; Human; Hyperalgesia; Life; Longitudinal Studies; Measures; Mechanics; Medical; Methods; Methylation; Methyltransferase; MicroRNAs; Modification; Mus; Neuropathy; Neurotransmitters; Opioid; Outpatients; Pain; Painless; Patient Self-Report; Pattern; Perception; Peripheral; Phenotype; Prevalence; Protocols documentation; Quality of life; Reporting; Research Design; Sampling; Schools; Science; Seasons; Sensory; Sickle Cell Anemia; Site; Stimulus; Symptoms; System; Temperature; Testing; Time; Tissues; Transgenic Mice; Visceral; Weather; Work; allodynia; base; calmodulin-dependent protein kinase II; central sensitization; chronic pain; comparative; dopamine D3 receptor; epigenetic marker; experience; health care service utilization; healthy volunteer; improved; inhibitor/antagonist; innovation; meetings; monoamine; public health relevance; response; sickling; tool; volunteer

DESCRIPTION (provided by applicant): Responsive to HL-133, our long-term goal is to improve pain control in adults with sickle cell disease (SCD) by phenotypic characterization of their chronic pain experiences. Often the etiology of SCD pain is thought to be only episodic, driven by mechanisms of somatic or visceral tissue damage, but it has become increasingly clear that adults with SCD also experience chronic pain. The lack of sufficient normative data for quantitative sensory testing (QST) measures in adults of African descent, however, is a barrier that must be addressed simultaneously with fundamental work to characterize chronic SCD pain phenotypes across time. We propose to determine normative QST values in 100 healthy African Americans to provide comparative data for an 18- month longitudinal study with repeated measures across seasons among 180 adult outpatients with SCD pain. We will characterize sensitization via quantitative sensory testing (QST) measures at three sites (2 painful, 1 non-painful) in adults with SCD pain; 4 times all 6 months apart. All subjects will complete well- validated, state-of- the-science self-report tools to characterize the perceived pain and its impac on quality of life and contribute samples for genetic and epigenetic analyses. Measures include: (1) mechanical QST (von Frey filaments), (2) thermal QST (cool/warm sensations, heat/cold pain thresholds), (3) self-report pain (PROMIS, PAINReportIt); (4) self-report neuropathic pain (S-LANSS, NPSI); (5) self-report quality of life (ASCQ-ME); and (6) genetic and epigenetic data (polymorphisms in the monoamine neurotransmitter systems, microRNA, and a global epigenetic marker LINE-1). Specific aims are: Aim 1. Based on normative values from 100 African American healthy volunteers, to compare the prevalence of pain sensitization in the healthy volunteers and 180 adults with SCD using mechanical and thermal stimulation of sensory fibers (A¿ [mechanical, von Frey QST], A-delta [cold QST], C [heat QST]). Hypothesis (HO): A significantly higher proportion of the SCD sample will report allodynia/hyperalgesia than healthy volunteers. Aim 2. From the 180 adults with SCD, to discover the chronic pain phenotype groups represented by the variability in the type of sensitization (none, central, peripheral, mixed) and pain characteristics (POMIS, PAINReportIt, S-LANSS, NPSI) and determine differences in self-report pain by the pain phenotypes. HO: Pain phenotypes will differ significantly on self-report pain (e.g., intensity, sensory, affective, pattern scores). Aim 3. Determine the genetic and epigenetic markers, pain treatment, environmental factors (season, temperature, wind), and quality of life scores associated with each phenotype across time among 180 adults with SCD. HO: Pain phenotypes with central or mixed sensitization will be associated with epigenetic markers (increased LINE-1 methylation, circulating let-7 microRNAs) and gene polymorphisms at the monoamine neurotransmitter network, high opioid doses, cold-related factors, and poorer quality of life. Findings will guide studies of adults to discover pain therapies for different pain phenotypes that effectively control chronic SCD pain and improve quality of life.

描述（由申请人提供）：对HL-133有反应，我们的长期目标是通过慢性疼痛经历的表型表征改善镰状细胞病（SCD）成人患者的疼痛控制。通常，SCD疼痛的病因被认为只是偶发性的，由躯体或内脏组织损伤的机制驱动，但越来越清楚的是，患有SCD的成年人也会经历慢性疼痛。然而，在非洲裔成年人中缺乏足够的定量感觉测试（QST）措施的规范性数据是一个障碍，必须与表征慢性SCD疼痛表型的基本工作同时解决。我们建议在100名健康的非洲裔美国人中确定规范的QST值，为180名患有SCD疼痛的成人门诊患者进行为期18个月的纵向研究提供比较数据。我们将通过定量感觉测试（QST）对SCD疼痛成人的3个部位（2个疼痛部位，1个非疼痛部位）进行致敏性测定;间隔6个月共4次。所有受试者都将完成经过充分验证的最先进的自我报告工具，以描述感知疼痛及其对生活质量的影响，并为遗传和表观遗传分析提供样本。措施包括：（1）机械QST（von Frey细丝），（2）热QST（冷/暖感觉，热/冷疼痛阈值），（3）自我报告疼痛（PROMIS，PAINReportIt）;（4）自我报告的神经性疼痛（5）生活质量自评量表（ASCQ-ME）;以及（6）遗传和表观遗传数据（单胺神经递质系统、microRNA和全局表观遗传标记LINE-1中的多态性）。具体目标是：目标1。基于100名非裔美国健康志愿者的标准值，比较健康志愿者和180名SCD成人中使用感觉纤维的机械和热刺激（A <$[机械，von Frey QST]，A-delta [冷QST]，C [热QST]）的疼痛致敏的患病率。假设（HO）：SCD样本中报告异常性疼痛/痛觉过敏的比例显著高于健康志愿者。目标2.从180例成人SCD患者中，发现由致敏类型（无、中枢、外周、混合）和疼痛特征（POMIS、PAINReportIt、S-LANSS、NPSI）的变异性代表的慢性疼痛表型组，并确定疼痛表型的自我报告疼痛的差异。HO：疼痛表型在自我报告的疼痛上会有显著差异（例如，强度、感觉、情感、模式分数）。目标3.确定180名SCD成人中与每种表型相关的遗传和表观遗传标记、疼痛治疗、环境因素（季节、温度、风）和生活质量评分。总部：中枢或混合致敏的疼痛表型与表观遗传标记物（LINE-1甲基化增加，循环let-7 microRNA）和单胺神经递质网络的基因多态性，高阿片类药物剂量，寒冷相关因素和较差的生活质量相关。研究结果将指导成人研究发现疼痛 治疗不同的疼痛表型，有效地控制慢性SCD疼痛和改善生活质量。