Disrupted Spatial and Temporal Nociceptive Filtering in Adolescents with and Risk for Overlapping Pain Conditions

患有重叠疼痛的青少年的空间和时间伤害性过滤被破坏以及存在重叠疼痛的风险

• 批准号: 10592728
• 负责人: Christopher D King
• 金额: $ 53.66万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592728
• 关键词: Abdominal Pain; Absence of pain sensation; Adolescent; Adult; Age; Awareness; Back; Behavioral; Childhood; Chronic; Clinic; Control Groups; Development; Dimensions; Early identification; Enrollment; Event; Female; Foundations; Future; Gastroenterology; Goals; Individual; Individual Differences; Knowledge; Life; Longevity; Medical center; Methods; Migraine; Musculoskeletal; Musculoskeletal Pain; Neuraxis; Neurosciences; Nociception; Pain; Pain Research; Pain management; Participant; Patients; Pattern; Phenotype; Pilot Projects; Positioning Attribute; Prevention; Public Health; Quality of life; Recording of previous events; Research; Rheumatology; Risk; Risk Factors; Sampling Studies; Sensory; Sleep disturbances; Stimulus; Stress; Testing; Time; United States National Institutes of Health; Youth; base; biopsychosocial; chronic pain; chronic painful condition; clinical infrastructure; clinically relevant; conditioned pain modulation; daily functioning; design; disability; experience; high risk; innovation; insight; longitudinal design; multidisciplinary; patient subsets; prevent; programs; prospective; psychosocial; recruit; screening; sex; somatosensory

PROJECT ABSTRACT While localized primary pain conditions are prevalent in youth, a significant subset of these patients experience multiple pain conditions and meet the criteria for chronic overlapping pain conditions (COPCs). COPCs have a marked negative impact on daily functioning and quality of life in youth and carry a high risk for continued pain and disability into adulthood. The underlying factors contributing to the development and persistence of COPCs in youth are unknown. The current proposal offers an innovative and previously unexplored approach to determine whether disruptions in spatial (concurrent noxious stimuli across the body) and temporal (noxious stimuli presented over time) filtering of nociceptive processing, reflecting pain amplification (e.g., increased facilitation and/or reduced inhibition), contribute to COPCs. Several quantitative sensory testing methods are uniquely positioned to probe disruptions in nociceptive filtering across spatial (spatial summation, SS; conditioned pain modulation, CPM) and temporal (temporal summation, TS; offset analgesia, OFA) domains. Our recent pilot studies found evidence for greater disruptions in spatial (CPM) and temporal (TS) filtering in youth with COPCs. Our primary objective is to determine if spatial and temporal filtering of nociceptive information differentiate youth with COPCs from those with localized pain and healthy controls and determine whether distinct profiles of disrupted nociceptive processing are associated with the transition of localized pain to COPCs. To accomplish this, the current study will leverage expertise and a vast clinical infrastructure (Migraine, Gastroenterology, Rheumatology and Pain Management clinics) at large pediatric medical center to enroll 140 youth with a localized pain condition (migraine, abdominal pain, local MSK), and 140 youth with COPC’s. We will also recruit 140 healthy youth to serve as a control group. Following initial phenotyping to delineate disruptions in spatial and temporal dimensions of nociceptive processing (Aim 1), participants will be assessed for changes in pain status (localized to COPCs) every three months for one year (Aim 2). In Aim 1, we hypothesize that youth with COPCs will show disrupted spatial (reflected by reduced CPM and enhanced SS) and temporal (reflected by enhanced TS and reduced OFA) processing compared to youth with localized pain and healthy controls. These findings will delineate specific disruptions of nociceptive processing in patients with COPCs. For Aim 2, we hypothesize that a subset of youth with localized pain and disrupted spatial and temporal filtering will develop COPCs. We will examine the stability of spatial and temporal filtering at clinically relevant timepoints (3-, 6-, and 12-months). We will also explore whether the disrupted filtering and the transition to COPCs are influenced by factors including concomitant treatments. Our research will provide the first insight into the presence and impact of disrupted nociceptive filtering related to COPCs and its naturalistic progression from localized pain. This information will be critical in identifying risk patterns that can be useful in prevention of progression to COPCs and mitigating long-term risk.

项目摘要 虽然局部原发性疼痛在年轻人中很普遍，但这些患者中有很大一部分经历过 多种疼痛状况并符合慢性重叠疼痛状况 (COPC) 的标准。 COPC 有一个 对青少年的日常功能和生活质量产生显着的负面影响，并且持续疼痛的风险很高 和成年后的残疾。影响其发展和持续的根本因素 青年时期的 COPC 尚不清楚。当前的提案提供了一种创新且以前未探索过的方法 确定空间（全身同时发生有害刺激）和时间（有害刺激）是否受到干扰 随着时间的推移呈现的刺激）过滤伤害性处理，反映疼痛放大（例如，增加 促进和/或减少抑制），有助于 COPC。几种定量感官测试方法 具有独特的定位，可以探测跨空间伤害感受过滤的破坏（空间求和，SS； 条件性疼痛调节（CPM）和时间（时间总和，TS；偏移镇痛，OFA）域。 我们最近的试点研究发现了空间 (CPM) 和时间 (TS) 过滤受到更大干扰的证据 患有 COPC 的年轻人。我们的主要目标是确定伤害感受的空间和时间过滤是否有效 信息将患有 COPC 的青少年与患有局部疼痛且控制健康的青少年区分开来，并确定 伤害性处理中断的不同特征是否与局部疼痛的转变有关 到 COPC。为了实现这一目标，当前的研究将利用专业知识和庞大的临床基础设施 （偏头痛、胃肠病学、风湿病学和疼痛管理诊所）在大型儿科医疗中心 招募 140 名患有局部疼痛（偏头痛、腹痛、局部 MSK）的青少年，以及 140 名患有局部疼痛的青少年 康普克的。我们还将招募140名健康青少年作为对照组。初始表型分析后 描绘伤害性处理的空间和时间维度的破坏（目标 1），参与者将 一年内每三个月评估一次疼痛状态的变化（仅限于 COPC）（目标 2）。在目标 1 中， 我们假设患有 COPC 的年轻人会表现出空间混乱（表现为 CPM 降低和 CPM 增强） 与具有局部化的青少年相比，SS）和时间（通过增强的 TS 和减少的 OFA）处理 疼痛和健康控制。这些发现将描述伤害感受处理的具体破坏 COPC 患者。对于目标 2，我们假设一部分患有局部疼痛和精神错乱的青少年 空间和时间过滤将发展 COPC。我们将检查空间和时间滤波的稳定性 在临床相关时间点（3、6 和 12 个月）。我们还将探讨是否中断的过滤和 向 COPC 的过渡受到包括伴随治疗在内的因素的影响。我们的研究将提供 首次深入了解与 COPC 及其相关的伤害性过滤中断的存在和影响 从局部疼痛自然进展。这些信息对于识别风险模式至关重要 可用于预防进展为 COPC 并降低长期风险。