Complex Persistant Pain Conditions: Unique & Shared Pathways of Vulnerability

复杂的持续性疼痛状况：独特

• 批准号: 8650335
• 负责人: WILLIAM MAIXNER
• 金额: $ 131.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650335
• 关键词: Address; Biological; Characteristics; Clinical; Complex; Coupled; Environmental Exposure; Epidemiologist; Etiology; Fatigue; Fibromyalgia; Functional disorder; Genetic; Genetic Polymorphism; Genetic Variation; Goals; Headache; Infection; Injury; Irritable Bowel Syndrome; Migraine; Molecular; Pain; Pathway interactions; Patients; Persistent pain; Physiological; Predisposition; Psychological Stress; Research Personnel; Risk Factors; Sleep; Temporomandibular Joint Disorders; chronic pain; programs; psychologic; psychological distress; vulvar vestibulitis

DESCRIPTION (provided by applicant): Complex persistent pain conditions (CPPCs) such as headache conditions, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and vulvar vestibulitis are high prevalent and shared or comorbid chronic pain conditions. There are two features of CPPCs that are fundamental to the aims and goals of this proposal: 1) the etiology of CPPCs is multifactorial and 2) the clinical manifestations of CPPCs are diverse. In this Program Project, we expect to identify a mosaic of risk factors for each of five CPPCs: fibromyalgia (FM), episodic migraine (EM), vulvar vestibulitis (VVS), irritable bowel syndrome (IBS), and temporomandibular joint disorders (TMD). Furthermore, we expect to characterize clusters of patients within each CPPC that vary significantly according to manifestations of their condition in addition to its painful characteristics (e.g., fatigue, dysfunction, sleep loss). Importantly, we expect some clusters of patients to be more alike across CPPCs than within any single CPPC, consistent with our view that there is some overlap in the manifestations of CPPCs. A unifying hypothesis integrating this Program is that multiple genetic factors, when coupled with environmental exposures (e.g. injury, infections, physical and psychological stress), increase the susceptibility to highly prevalent CPPCs by enhancing pain sensitivity and/or increasing psychological distress. To address the aims and goals of the subprojects and cores described in this application, a group of accomplished pain clinicians, pain researchers, psychophysiologists, molecular and cellular geneticists, biostatisticians and epidemiologists have been brought together to form this Program. Studies proposed in this Program Project application seek to identify the psychological and physiological risk factors, clusters, and associated genetic polymorphisms, that influence pain amplification and psychological profiles in enrollees who have established CPPDs. Additionally, the proposed studies seek to characterize the biological pathways through which these genetic variations causally influence CPPCs.

描述（由申请方提供）：复杂持续性疼痛病症（CPPC），如头痛病症、纤维肌痛、颞下颌关节紊乱病、肠易激综合征和外阴前庭炎，是高流行率和共享或共病的慢性疼痛病症。CPPC的两个特征对于本提案的目的和目标至关重要：1）CPPC的病因是多因素的，2）CPPC的临床表现多种多样。在这个项目中，我们希望确定五种CPPC的风险因素：纤维肌痛（FM），阵发性偏头痛（EM），外阴前庭炎（VVS），肠易激综合征（IBS）和颞下颌关节紊乱病（TMD）。此外，我们希望描述每个CPPC中的患者群的特征，这些患者群根据其病情的表现以及疼痛特征（例如，疲劳、功能障碍、睡眠不足）。重要的是，我们预计在CPPC之间的一些患者群比任何单一CPPC内的患者群更相似，这与我们认为CPPC的表现存在一些重叠的观点一致。整合该计划的统一假设是，多种遗传因素，当与环境暴露（例如损伤，感染，身体和心理压力）相结合时，通过增强疼痛敏感性和/或增加心理困扰，增加了对高度流行的CPPC的易感性。为了解决本申请中描述的子项目和核心的目的和目标，一组有成就的疼痛临床医生，疼痛研究人员，心理生理学家，分子和细胞遗传学家，生物统计学家和流行病学家聚集在一起，形成了这个计划。 本计划项目申请中提出的研究旨在确定心理和生理风险因素，集群和相关的遗传多态性，这些因素影响已建立CPPD的注册者的疼痛放大和心理特征。此外，拟议的研究旨在表征这些遗传变异因果影响CPPC的生物学途径。

项目成果

Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia.

MU阿片类剪接变体MOR-1K有助于阿片类药物诱导的痛觉过敏的发展。

• DOI: 10.1371/journal.pone.0135711
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Oladosu FA;Conrad MS;O'Buckley SC;Rashid NU;Slade GD;Nackley AG
• 通讯作者: Nackley AG

Relationship between temporomandibular disorders, widespread palpation tenderness, and multiple pain conditions: a case-control study.

颞下颌疾病，广泛的触诊压痛与多种疼痛状况之间的关系：病例对照研究。

• DOI: 10.1016/j.jpain.2012.07.011
• 发表时间: 2012-10
• 期刊: JOURNAL OF PAIN
• 影响因子: 4
• 作者: Chen, Hong;Slade, Gary;Lim, Pei Feng;Miller, Vanessa;Maixner, William;Diatchenko, Luda
• 通讯作者: Diatchenko, Luda

Elucidation of mu-Opioid Gene Structure: How Genetics Can Help Predict Responses to Opioids.

• DOI: 10.1016/j.eujps.2011.08.022
• 发表时间: 2011-11-11
• 期刊: European journal of pain supplements

Bilateral accessory breast tissue of the vulva: a case report introducing a novel labiaplasty technique.

外阴双侧副乳组织：介绍新型阴唇整形术技术的病例报告。

• DOI: 10.1097/sap.0b013e31827ead39
• 发表时间: 2013
• 期刊: Annals of plastic surgery
• 影响因子: 1.5
• 作者: Wagner,IJanelle;Damitz,LynnA;Carey,Erin;Zolnoun,Denniz
• 通讯作者: Zolnoun,Denniz

Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study.

• DOI: 10.1016/j.jpain.2011.08.005
• 发表时间: 2011-11
• 期刊: The journal of pain
• 作者: Smith SB;Maixner DW;Greenspan JD;Dubner R;Fillingim RB;Ohrbach R;Knott C;Slade GD;Bair E;Gibson DG;Zaykin DV;Weir BS;Maixner W;Diatchenko L
• 通讯作者: Diatchenko L