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

描述（由申请人提供）：我们对HL-133有反应，我们的长期目标是通过慢性疼痛经历的表型特征来改善成人镰状细胞病（SCD）的疼痛控制。SCD疼痛的病因通常被认为是偶发性的，由躯体或内脏组织损伤的机制驱动，但越来越清楚的是，成人SCD患者也会经历慢性疼痛。然而，非洲裔成年人定量感官测试（QST）措施缺乏足够的规范数据，这是一个必须与长期表征慢性SCD疼痛表型的基础工作同时解决的障碍。我们建议确定100名健康非裔美国人的标准QST值，为180名患有SCD疼痛的成年门诊患者进行为期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）在三个部位（2个疼痛，1个非疼痛）测量成人SCD疼痛的致敏性；相隔6个月的4次。所有受试者将完成有效的、先进的自我报告工具，以描述感知到的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。测量方法包括：(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, painreporttit）；(4)自述神经性疼痛（S-LANSS， NPSI）；(5)自我报告生活质量（ASCQ-ME）；(6)遗传和表观遗传数据（单胺类神经递质系统、microRNA和全局表观遗传标记LINE-1的多态性）。具体目标是：目标1。以100名非裔美国健康志愿者的正常值为基础，比较机械和热刺激感觉纤维（A¿[mechanical, von Frey QST], A-delta [cold QST], C [heat QST]）对健康志愿者和180名SCD成人疼痛致敏率的影响。假设（HO）：与健康志愿者相比，SCD样本中报告异常性痛觉/痛觉过敏的比例明显更高。目标2。从180例成人SCD患者中，发现以致敏类型（无致敏型、中枢型、外周型、混合型）和疼痛特征（POMIS、painreporttit、S-LANSS、NPSI）的变异性为代表的慢性疼痛表型组，并通过疼痛表型确定自述疼痛的差异。HO：疼痛表型在自我报告的疼痛（如强度、感觉、情感、模式得分）上有显著差异。目标3。确定180名成年SCD患者的遗传和表观遗传标记、疼痛治疗、环境因素（季节、温度、风）以及与每种表型相关的生活质量评分。HO：中枢或混合致敏的疼痛表型将与表观遗传标记（LINE-1甲基化增加，循环let-7 microrna）和单胺神经递质网络基因多态性、高阿片类药物剂量、寒冷相关因素和较差的生活质量相关。研究结果将指导对成人疼痛的研究

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.