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

基本信息

批准号：
9265070
负责人：
Luana Colloca
金额：
$ 54.66万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
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/9265070
关键词：
Absence of pain sensation Address Adherence Affect Affective American Amygdaloid structure Analgesics Area Behavioral 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 Neurotics Opioid Receptor Orofacial Pain Outcome Pain Pain management Pathway interactions Patients Perception Personality Pharmacogenomics Pharmacological Treatment Pharmacology 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 imaging approach mu opioid receptors negative affect neurobiological mechanism neurotransmission new therapeutic target novel novel strategies opioid use psychologic public health relevance response sensor social success therapy outcome trait treatment planning treatment responders

项目摘要

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（由申请人提供）：慢性疼痛影响着大量美国人，每年造成约 6000 亿美元的损失，特别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慢性疼痛状况，影响约 100 亿美国人。 6% 的人最近的研究表明，遗传因素在慢性疼痛的敏感性、调节和易感性方面发挥着重要作用，而有些人的慢性疼痛经历差异很大。不同的人对治疗干预的反应也有很大差异；对于某些人来说，药物治疗非常有效，而对于另一些人来说，临床疼痛结果的变化幅度高达 50%。已被证明是继发于期望引起的镇痛，其定义为个体对治疗干预的感知所导致的疼痛减轻。换句话说，患者的期望可以调节个体的疼痛体验、处理和反应。疼痛因此，更好地了解遗传对预期诱导的镇痛的影响以及激活内源性抑制系统的倾向性的变化对于优化疼痛治疗至关重要，我们开发了一种新颖的综合遗传、行为和成像方法来研究遗传变异的作用。关于 TMD 患者期望诱发镇痛的行为、心理和神经机制我们致力于以下具体目标： 1. 检验候选基因变异与预测慢性口面部疼痛的期望诱发镇痛相关的假设。 2. 检验以下假设：无论疾病的严重程度如何，个体心理特征是预期引起的镇痛的复杂遗传调节的独特调节因素；3. 检验特定（已识别）基因的变异可预测预期的假设；前额叶和边缘区域诱导的镇痛和相关神经变化将作为预测主观（例如疼痛报告）和客观（例如神经元）反应的重要标记。我们期望：a）提供一个新的框架来研究慢性口面部疼痛的药物基因组学，b）确定可用于开发新治疗靶点的遗传标记和机制。策略，并最终 c) 确定哪些患者最有可能对特定治疗产生反应。