Effects of cumulative stress and change in pain regulation on risk of chronic TMD

累积压力和疼痛调节变化对慢性 TMD 风险的影响

• 批准号: 8282086
• 负责人: Gary Douglas Slade
• 金额: $ 14.59万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282086
• 关键词: Acute; Address; Adrenergic Agents; Advisory Committees; American; Arthralgia; Award; Blood specimen; Characteristics; Chronic; Chronic stress; Clinical assessments; Cohort Studies; DNA; Data; Data Analyses; Data Collection; Data Set; Development; Diagnosis; Enrollment; Enzymes; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Epinephrine; Etiology; Evaluation; Functional disorder; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Growth; Health; Investigation; Label; Life Cycle Stages; Measures; Methods; Modeling; Myalgia; National Institute of Dental and Craniofacial Research; Neurotransmitter Receptor; Norepinephrine; Orofacial Pain; Pain; Pain Measurement; Pathway interactions; Pattern; Perception; Phenotype; Physiological; Psychological Stress; Questionnaires; Recruitment Activity; Regulation; Risk; Risk Assessment; Risk Factors; Series; Severities; Site; Stress; Symptoms; Synapses; System; Temporomandibular Joint Disorders; Testing; Time; United States National Institutes of Health; Update; Variant; adrenergic; aged; base; chronic pain; cohort; experience; follow-up; gene environment interaction; innovation; prospective; response

DESCRIPTION (provided by applicant): Each year, millions of Americans develop painful temporomandibular disorders (TMD), and symptoms become chronic for as many as one third of them. Yet, little is known about the antecedents of chronic TMD; instead, the best predictors of chronic TMD are characteristics of pain assessed when the condition has already developed. We propose to analyze data collected before, during and after onset of TMD to investigate how antecedent risk factors unfold over time to influence risk of chronic TMD. We hypothesize that repeated psychological stress elicits changes in pain regulatory systems, causing transition from acute to chronic pain in genetically-susceptible people. In response to PAR-09-182, we plan to use existing data in three add-on studies of the multi-site OPPERA prospective cohort study (Orofacial Pain, Prospective Evaluation and Risk Assessment; NIH/NIDCR U01-DE017018). OPPERA enrolled, 3,263 people aged 18-44 years who were examined at baseline to confirm absence of TMD. They also completed questionnaires, underwent physiologic testing of pain regulatory systems (i.e. pain sensitivity and autonomic function), and they provided a sample of blood from which DNA was extracted for genotyping. During the average 3-year follow-up period, quarterly health update questionnaires identified people who developed symptoms, and 258 of them were diagnosed with first-onset TMD. This proposal will analyze three add-on data-collections. 1) The Perceived Stress Scale was added to the quarterly health update questionnaire, providing 31,127 repeated measures of psychological stress among the 2,743 people retained in the cohort. 2) Baseline phenotypic measures were repeated when TMD was first diagnosed in the 258 incident cases. Six months later, the same measures again were repeated, and 85 people were diagnosed with chronic TMD (i.e. duration >6 months). 3) For each incident case, a matched control was selected, and equivalent data were collected at the time the matched case was diagnosed, and six months later. Life course epidemiologic methods will be used to analyze how these repeated measures of perceived stress and pain regulation unfold against the backdrop of people's genetic predisposition, focusing on genes encoding enzymes, neurotransmitters and receptors of the adrenergic system that regulate pain perception. Mixed models for repeated measures and latent growth curve methods will evaluate two qualitatively different pathways by which these risk factors might exert combined effects on risk of chronic TMD: a) an independent risk pathway, in which risk factors exert independent, additive effects; b) an accumulation pathway, in which genes give rise to a cluster of factors involving psychological stress, pain sensitivity and altered autonomic function. To guard against type I error, a sequential set of analyses will restrict tests for gene x phenotype interactions. Based on our preliminary analysis, this strategy provides good power to detect main effects of phenotypes (>0.99) to and sufficient power to detect gene x case-status interactions (0.84) and gene x cumulative stress interactions (0.64). PUBLIC HEALTH RELEVANCE: Each year, millions of Americans develop painful temporomandibular disorders (TMD), and as many as one third of them will develop chronic TMD, lasting more than six months. This project will investigate experiences occurring before, during and after first-onset of TMD to determine how acute TMD progresses to chronic pain. Using existing data already collected from 2,743 over a three-year average period of follow-up we analyze influences of psychological stress, pain regulatory systems and genes on development of chronic TMD.

描述（由申请人提供）：每年，数百万美国人患上疼痛性颞下颌关节紊乱病（TMD），其中三分之一的人的症状变为慢性。然而，对慢性TMD的前因知之甚少;相反，慢性TMD的最佳预测因子是在病情已经发展时评估的疼痛特征。我们建议分析收集的数据之前，期间和发病后的TMD调查如何随着时间的推移，影响慢性TMD的风险的前因危险因素展开。我们假设，反复的心理压力会导致疼痛调节系统的变化，导致遗传易感人群从急性疼痛转变为慢性疼痛。作为对PAR-09-182的回应，我们计划在多中心OPPERA前瞻性队列研究（口面部疼痛、前瞻性评价和风险评估; NIH/NIDCR U 01-DE 017018）的三项附加研究中使用现有数据。OPPERA招募了3，263名年龄在18-44岁之间的人，他们在基线时接受了检查，以确认没有TMD。他们还完成了问卷调查，接受了疼痛调节系统的生理测试（即疼痛敏感性和自主神经功能），并提供了血液样本，从中提取DNA进行基因分型。在平均3年的随访期间，季度健康更新问卷确定了出现症状的人，其中258人被诊断为首发TMD。本提案将分析三个附加数据收集。1)感知压力量表被添加到季度健康更新问卷中，在队列中保留的2，743人中提供了31，127次重复的心理压力测量。2)在258例发病病例中，当TMD首次被诊断时，重复基线表型测量。6个月后，再次重复同样的测量，85人被诊断为慢性TMD（即持续时间>6个月）。3)对于每个事件病例，选择匹配的对照，并在匹配病例诊断时和六个月后收集等效数据。生命过程流行病学方法将被用来分析这些感知压力和疼痛调节的重复测量如何在人们的遗传易感性的背景下展开，重点是编码酶的基因，调节疼痛感知的肾上腺素能系统的神经递质和受体。重复测量和潜在生长曲线方法的混合模型将评估两种性质不同的途径，这些危险因素可能通过这两种途径对慢性TMD的风险产生联合效应：a）独立的风险途径，其中危险因素产生独立的累加效应; B）积累途径，其中基因引起一组涉及心理应激、疼痛敏感性和自主神经功能改变的因素。为了防止I型错误，一组连续的分析将限制基因x表型相互作用的测试。基于我们的初步分析，该策略提供了良好的功效来检测表型的主效应（>0.99），并提供了足够的功效来检测基因x病例-状态相互作用（0.84）和基因x累积应激相互作用（0.64）。 公共卫生关系：每年有数百万美国人患上疼痛的颞下颌关节紊乱病（TMD），其中多达三分之一的人会患上慢性TMD，持续时间超过6个月。本项目将调查TMD首次发作之前、期间和之后的经历，以确定急性TMD如何发展为慢性疼痛。使用现有的数据已经收集了2,743超过三年的平均随访期，我们分析了心理压力，疼痛调节系统和基因对慢性TMD发展的影响。