Genetic and Psychosocial Influences on Transition to Chronic TMD and Related Pain

遗传和社会心理对慢性 TMD 及相关疼痛的影响

• 批准号: 8713244
• 负责人: LUDA DIATCHENKO
• 金额: $ 289.01万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8713244
• 关键词: Abdomen; Acute; Acute Pain; Address; Adult; Affect; American; Characteristics; Chronic; Clinical; Cohort Analysis; Cohort Studies; DNA; Data; Development; Disease; Enrollment; Etiology; Evaluation; Event; Exons; Fibrinogen; Functional disorder; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genital system; Genome; Genotype; Headache; Health Care Costs; Individual; Irritable Bowel Syndrome; Knowledge; Low Back Pain; Measures; Minor; National Institute of Dental and Craniofacial Research; Orofacial Pain; Pain; Participant; Patients; Persistent pain; Phase; Phenotype; Physiological; Psychosocial Influences; Public Health; Quality of life; Recording of previous events; Recruitment Activity; Relative (related person); Research Design; Resolution; Risk; Risk Assessment; Risk Factors; Sampling; Sensory; Site; Symptoms; Temporomandibular Joint Disorders; Time; United States National Institutes of Health; base; case control; chronic pain; clinically relevant; cohort; design; experience; follow-up; genetic association; genetic variant; genome wide association study; genotyping technology; member; novel; prospective; psychologic; psychological distress; public health relevance

DESCRIPTION (provided by applicant): While virtually everyone experiences acute pain at some time, it is chronic pain that exacts a profound burden on the public health, reducing quality of life for tens of millions Americans, and incurring substantial health care costs. Yet little is known about mechanisms that cause a transition from acute to chronic pain; subsequently, event the best of treatments have limited efficacy. One likely clue regarding etiology is that patients who have one form of chronic pain often experience chronic pain elsewhere in the body. In this project, we hypothesize that the transition from acute to chronic pain and the development of multiple chronic pain conditions, are caused by specific constellations of genetic variants and phenotypic risk factors (ie. psychological distress, pain amplification and clinical pain characteristics). This hypothesis is based on our studies of temporomandibular disorder (TMD) in the multi-site OPPERA project (Orofacial Pain, Prospective Evaluation and Risk Assessment; NIH/NIDCR U01-DE017018). In 2006-08, we enrolled 3,263 healthy adults, 233 of whom developed acute TMD during the 3-year follow-up period. Risk factors for acute TMD differed conspicuously from genetic and phenotypic risk factors for chronic TMD. Furthermore, 86% of chronic TMD cases had one or more of four chronic, idiopathic pain conditions: headache (HA), low back pain (LBP), irritable bowel syndrome (IBS) or widespread bodily pain (WBP). In this competitive renewal application, we propose three new aims designed to reveal novel information regarding the etiology and pathophysiology of chronic pain. Aim 1: To identify phenotypes and genotypes that predict risk of transition from acute TMD to chronic TMD, we will enroll a new cohort of 1,000 adults who have acute TMD, following them for six months to identify an expected 400 who progress to chronic TMD. Aim 2 will identify risk factors for one or more of five: idiopathic pain conditions (IPCs): TMD, HA, LBP, IBS and/or WBP. Follow-up assessments will be conducted among people in the OPPERA-I prospective cohort study, identifying an expected 640 people who have ¿1 IPC. Existing phenotypes and genotypes measured at baseline will be used to predict risk of 1 IPC vs. ¿2 IPCs relative to controls. Aim 3 will identify genetic variants associated with chronic TMD. A discovery-phase genome wide association study (GWAS) will use existing DNA from 1,000 OPPERA-I chronic TMD cases and 1,000 OPPERA-I controls. Replication will use a new cohort of n=1,000 chronic TMD cases and n=1,000 controls. Those findings will be contrasted with GWAS analysis of the cohort for Aim 1 to identify genes that contribute differentially to acute and chronic TMD. Based on these findings and validated associations from other studies, twelve genes will be selected for exon sequencing of rare genetic variants. Knowledge generated from these proposed studies will have a significant impact on scientific understanding of risk factors for multiple, overlapping pai conditions. Moreover, the findings will be of direct benefit for clinicians and for their patients, elucidating mechanisms underlying chronic and idiopathic pain in people with TMD.

描述（由适用提供）：虽然几乎每个人在某个时候都经历了急性疼痛，但正是慢性疼痛恰好在公共卫生上燃烧，降低了数千万美国人的生活质量，并导致了中学保健费用。然而，关于导致从急性到慢性疼痛过渡的机制知之甚少。随后，事件最好的治疗效率有限。考虑病因的一种可能的线索是，患有一种慢性疼痛的患者经常在体内其他地方经历慢性疼痛。在这个项目中，我们假设从急性到慢性疼痛以及多种慢性疼痛状况的发展是由遗传变异和表型危险因素的特定星座（即心理困扰，疼痛扩增和临床疼痛特征）引起的。该假设基于我们对多站点OPPera项目（口面痛，前瞻性评估和风险评估的颞下颌疾病（TMD）的研究； NIH/NIDCR U01-DE017018）。在2006 - 08年，我们招募了3,263名健康成年人，其中233名在3年的随访期内发展了急性TMD。急性TMD的危险因素与慢性TMD的遗传和表型危险因素的明显明显不同。此外，有86％的慢性TMD病例患有四个慢性特发性疼痛状况中的一个或多个：头部（HA），下背痛（LBP），肠易激综合征（IBS）或广泛的身体疼痛（WBP）。在这种竞争性更新应用中，我们提出了三个新的目标，旨在揭示有关慢性疼痛的病因和病理生理学的新信息。目标1：确定预测从急性TMD过渡到慢性TMD的过渡风险的表型和基因型，我们将招募一个有急性TMD的1,000名成年人组成的新队列，然后跟随它们六个月以识别出预期的400人，他们进展到慢性TMD。 AIM 2将确定五个中一个或多个的危险因素：特发性疼痛状况（IPC）：TMD，HA，LBP，IBS，IBS和/或WBP。在Oppera-i前瞻性队列研究中，将在人们之间进行后续评估，并确定有640名IPC的人。在基线时测量的现有表型和基因型将用于预测1 IPC与2个IPC相对于对照组的风险。 AIM 3将识别与慢性TMD相关的遗传变异。一项发现阶段基因组广泛的关联研究（GWAS）将使用1,000个Oppera-I慢性TMD病例和1,000个Oppera-I对照组中的现有DNA。复制将使用N = 1,000个Chromic TMD病例和n = 1,000个对照组的新队列。这些发现将与AIM 1的GWAS分析形成鲜明对比，以鉴定对急性和慢性TMD有不同贡献的基因。基于这些发现和其他研究的验证关联，将选择十二个基因进行稀有遗传变异的外显子测序。这些拟议的研究产生的知识将对对多个重叠的PADI条件的风险因素的科学理解产生重大影响。此外，对临床医生及其患者的发现将是直接的好处 阐明TMD患者慢性和特发性疼痛的基础机制。