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: 8440291
• 负责人: Gary Douglas Slade
• 金额: $ 14万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8440291
• 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).

描述（由申请人提供）：每年，数以百万计的美国人患有疼痛性颞下颌疾病（TMD），其中多达三分之一的人的症状变成了慢性。然而，人们对慢性 TMD 的前因知之甚少。相反，慢性 TMD 的最佳预测因素是在病情已经发展时评估的疼痛特征。我们建议分析 TMD 发病前、发病期间和发病后收集的数据，以研究先前的危险因素如何随时间推移而影响慢性 TMD 的风险。我们假设，反复的心理压力会引起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。为了响应 PAR-09-182，我们计划在多中心 OPPERA 前瞻性队列研究的三项附加研究中使用现有数据（口腔疼痛、前瞻性评估和风险评估；NIH/NIDCR U01-DE017018）。 OPPERA 招募了 3,263 名年龄在 18-44 岁之间的人，他们接受了基线检查，以确认不存在 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 年的随访期内，每季度进行一次健康更新调查问卷，确定出现症状的人，其中 258 人被诊断为初发 TMD。该提案将分析三个附加数据集合。 1) 在季度健康更新调查问卷中添加了感知压力量表，为队列中保留的 2,743 人提供了 31,127 项重复的心理压力测量结果。 2) 在 258 例病例中首次诊断 TMD 时，重复了基线表型测量。六个月后，再次重复相同的措施，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。生命全程流行病学方法将用于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倾向背景下展开，重点关注编码调节疼痛感知的肾上腺素能系统酶、神经递质和受体的基因。重复测量和潜在生长曲线方法的混合模型将评估这些风险因素可能对慢性 TMD 风险产生综合影响的两种性质不同的途径： a) 独立风险途径，其中风险因素发挥独立的累加效应； b) 积累途径，其中基因产生一系列涉及心理压力、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。根据我们的初步分析，该策略提供了良好的功效来检测表型的主要影响（>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）。