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，成千上万的美国人患有痛苦的颞下颌疾病（TMD），并且症状在其中多达三分之一的人慢性病。然而，关于慢性TMD的先例知之甚少。取而代之的是，慢性TMD的最佳预测因素是何时已经发展出疼痛的特征。我们建议分析在TMD发作之前，之中和之后收集的数据，以研究随着时间的推移而影响的危险因素如何影响慢性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，从而导致遗传敏感的人从急性到慢性疼痛的过渡。为了响应PAR-09-182，我们计划在多站点Oppera前瞻性队列研究的三个附加研究中使用现有数据（口面疼痛，前瞻性评估和风险评估； NIH/NIH/NIDCR U01-DE017018）。 Oppera招募了3,263名18-44岁的人，他们在基线时进行了检查以确认缺乏TMD。他们还完成了问卷调查，对疼痛调节系统的生理测试（即疼痛敏感性和自主功能）进行了生理测试，并提供了一个血液样本，从中提取了DNA来进行基因分型。在平均3年的随访期间，季度健康更新问卷确定了患有症状的人，其中258名被诊断出患有第一次抗议TMD。该建议将分析三个附加数据收集。 1）感知到的压力量表已添加到季度健康更新问卷中，在保留在该队列中的2,743人中，有31,127个重复的心理压力度量。 2）在258例事件病例中首次诊断出TMD时，重复基线表型措施。六个月后，再次重复同样的措施，并诊断出85人患有慢性TMD（即持续时间> 6个月）。 3）对于每种事件，选择了匹配的控制，并在诊断出匹配的情况时收集了等效数据，并在六个月后收集。生命过程流行病学方法将用于分析人们如何在人们的遗传易感性的背景下展开这些感知到的压力和疼痛调节的方法，重点是编码酶，神经递质和受体的基因，以及调节疼痛感感知的肾上腺疗法系统的受体。重复测量和潜在生长曲线方法的混合模型将评估两种质量不同的途径，通过这些途径，这些风险因素可能会对慢性TMD风险产生综合影响：a）独立风险途径，其中风险因素具有独立的，附加的影响； b）一种积累途径，其中基因引起了一系列涉及心理压力，疼痛敏感性和自主功能改变的因素。为了防止I型错误，一组顺序分析将限制基因X表型相互作用的测试。基于我们的初步分析，该策略为检测表型（> 0.99）的主要作用提供了良好的力量，并有足够的能力来检测基因x病例态相互作用（0.84）和基因X累积应力相互作用（0.64）。