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

描述(由申请人提供)：响应HL-133，我们的长期目标是通过对他们的慢性疼痛经历的表型特征来改善患有镰状细胞病(SCD)的成年人的疼痛控制。SCD疼痛的病因通常被认为只是间歇性的，由躯体或内脏组织损伤机制驱动，但越来越清楚的是，SCD成人也经历慢性疼痛。然而，缺乏足够的标准数据用于非洲裔成年人的定量感觉测试(QST)测量，这是一个必须与基础工作同时解决的障碍，以表征不同时间的慢性SCD疼痛表型。我们建议确定100名健康的非裔美国人的标准QST值，为对180名患有SCD疼痛的成年门诊患者进行为期18个月的跨季节重复测量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个疼痛部位，1个非疼痛部位)对患有SCD疼痛的成人患者的敏感度进行表征；相隔6个月共4次。所有受试者将完成经过充分验证的、最先进的自我报告工具，以表征感知到的疼痛及其对生活质量的影响，并为遗传学和表观遗传学分析提供样本。测量包括：(1)机械QST(von Frey细丝)，(2)热QST(冷/暖感觉，热/冷痛阈值)，(3)自我报告疼痛(PROMIS，PAINReportIt)；(4)神经病理性疼痛自我报告(S-LANSS，NPSI)；(5)自我报告生活质量(ASCQ-ME)；以及(6)遗传和表观遗传学数据(单胺类神经递质系统、microRNA和全球表观遗传标记LINE-1的多态性)。目的：1.以100名非裔美国人健康志愿者的正常值为基础，比较机械刺激和热刺激感觉神经纤维(A�[机械，von Frey QST]、A-Delta[冷QST]、C[热QST])在健康志愿者和成人SCD患者中的痛敏化发生率。假设(HO)：与健康志愿者相比，SCD样本中报告痛觉过敏/痛觉过敏的比例明显更高。目的2.从180例SCD患者中发现慢性疼痛表型组，表现为敏化类型(无、中枢性、外周性、混合性)和疼痛特征(POMIS、PAINReportIt、S-LANSS、NPSI)的差异，并通过疼痛表型确定自我报告疼痛的差异。HO：疼痛表型在自我报告疼痛(例如，强度、感觉、情感、模式得分)方面会有很大的不同。目的3.在180例成人SCD患者中，确定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。HO：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，循环中的let-7微RNA)和单胺类神经递质网络的基因多态、高阿片类药物剂量、寒冷相关因素和较差的生活质量有关。这些发现将指导对成年人的研究以发现疼痛 针对不同疼痛表型的治疗，有效控制慢性SCD疼痛，提高生活质量。

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.