Chronic orofacial pain: genetics, cognitive-emotional factors, and endogenous modulatory systems

慢性口面部疼痛：遗传、认知情绪因素和内源性调节系统

• 批准号: 9098079
• 负责人: Luana Colloca
• 金额: $ 49.83万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-20 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9098079
• 关键词: Absence of pain sensation; Accounting; Address; Adherence; Affect; Affective; American; Amygdaloid structure; Analgesics; Area; Behavioral; Behavioral Genetics; Behavioral Model; Biological; Brain; Brain region; Candidate Disease Gene; Chronic; Chronic Disease; Clinical; Cognitive; Complex; Data; Development; Economic Burden; Economics; Expectancy; Exposure to; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Genes; Genetic; Genetic Markers; Genetic Variation; Genotype; Human; Image; Individual; Knowledge; Link; Mediating; Modeling; Mutation; NTRK2 gene; Naloxone; Narcotic Antagonists; Negative Valence; Neurons; Neurotic Disorders; Opioid Receptor; Orofacial Pain; Outcome; Pain; Pain management; Pathway interactions; Patients; Perception; Personality; Pharmacogenomics; Pharmacological Treatment; Phenotype; Placebos; Play; Population; Positive Valence; Positron-Emission Tomography; Predisposition; Prefrontal Cortex; Process; Public Health; Recording of previous events; Reporting; Rewards; Risk Factors; Role; Secondary to; Severities; Severity of illness; Shapes; System; Temporomandibular Joint Disorders; Testing; Therapeutic; Therapeutic Intervention; Time; Translating; United States; Variant; Ventral Striatum; base; behavioral study; chronic pain; clinical phenotype; coping; cost; emotional factor; endogenous opioids; endophenotype; experience; genetic predictors; genetic variant; negative affect; neurobiological mechanism; neurotransmission; new therapeutic target; novel; novel strategies; psychologic; public health relevance; response; social; success; therapy outcome; trait; treatment planning; treatment responders

 DESCRIPTION (provided by applicant): Chronic pain affects a large number of Americans, costing an estimated $600 billion annually. In particular, temporomandibular joint disorder (TMD), a complex chronic pain condition influenced by biological, psychological, environmental and social factors affects about 6% of the population. Recent studies suggest that genetics plays an important role in pain sensitivity, modulation and susceptibility to the development of chronic pain and TMD. Individual chronic pain experience is highly variable; some people are mildly affected, while others suffer debilitating dysfunction. Individuals also vary substantially n their responses to therapeutic interventions; for some, pharmacological treatments are highly efficacious while in others only modest reductions in pain occur. Up to 50% of the variability in clinical pain outcomes has been shown to be secondary to expectancy-induced analgesia, defined as the reduction in pain in an individual that results from his or her perception of the therapeutic intervention. In other words, patients' expectancies can modulate the individual pain experience, processing and response to pain treatments. Therefore, better understanding of the genetic effects on expectancy-induced analgesia and the variability in proneness to activate endogenous inhibitory systems is critical to optimize pain treatments. We developed a novel comprehensive genetic, behavioral and imaging approach to study the role of genetic variations on behavioral, psychological and neuronal mechanisms of expectancy-induced analgesia in patients with TMD. We address the following specific aims: 1. Test the hypothesis that variants in candidate genes are associated with expectancy-induced analgesia predicting chronic orofacial pain endophenotypes; 2. Test the hypothesis that individual psychological traits are unique modulators of the complex genetic moderation of expectancy-induced analgesia, regardless of the severity of the disease; and 3. Test the hypothesis that variations in the specific (identified) genes predict expectancy-induced analgesia and related neuronal changes in the prefrontal and limbic areas. The identified genotypes will serve as important markers to predict subjective (e.g. pain reports) and objective (e.g. neuronal) responses to expectancy-induced analgesia while controlling for modulatory effects of distinct personalities. We anticipate: a) to provide a new framework to study the pharmacogenomics of chronic orofacial pain, b) to identify genetic markers and mechanisms that can be used to develop new therapeutic targets and strategies and ultimately, c) to determine which patients are most likely to respond to specific treatments.

 描述(申请人提供)：慢性疼痛影响了大量美国人，估计每年造成6000亿美元的损失。尤其是颞下颌关节紊乱病(TMD)，这是一种受生物、心理、环境和社会因素影响的复杂的慢性疼痛状况，约有6%的人口受到影响。最近的研究表明，遗传学在慢性疼痛和TMD的疼痛敏感性、调节和易感性方面起着重要作用。个人的慢性疼痛体验是高度可变的；一些人受到轻微影响，而另一些人则遭受衰弱功能障碍。个体对治疗干预的反应也有很大的不同；对一些人来说，药物治疗是非常有效的，而在另一些人中，疼痛只有轻微的减轻。临床疼痛结果中高达50%的变异性被证明是预期诱导止痛的次要因素，预期诱导止痛的定义是个人由于对治疗干预的感知而导致的疼痛减轻。换句话说，患者的期望可以调节个体的疼痛体验、处理和对疼痛治疗的反应。因此，更好地了解预期镇痛的遗传效应以及激活内源性抑制系统的倾向性的差异，对于优化疼痛治疗至关重要。我们开发了一种新的综合遗传、行为和成像方法来研究遗传变异在TMD患者期望诱导镇痛的行为、心理和神经机制中的作用。我们致力于以下具体目标：1.测试候选基因的变异与预期诱导镇痛相关的假设，预测慢性口面部疼痛的内在表型；2.测试个体心理特征是期望诱导镇痛复杂遗传调节的独特调节者的假设，而不管疾病的严重程度；以及3.测试特定(已识别的)基因变异预测预期诱导镇痛以及前额叶和边缘区域相关神经元变化的假设。确定的基因类型将作为重要的标记来预测对预期诱导的止痛的主观(例如疼痛报告)和客观(例如神经元)反应，同时控制不同个性的调节效应。我们期望：a)为研究慢性口腔面部疼痛的药物基因组学提供一个新的框架，b)确定可用于开发新的治疗目标和策略的遗传标记和机制，并最终确定哪些患者最有可能对特定的治疗产生反应。