Secondary Analysis and Integration of Existing Data Related to Chronic Orofacial Pain and Placebo Effects - Administrative Supplement

与慢性口面部疼痛和安慰剂效应相关的现有数据的二次分析和整合 - 行政补充

• 批准号: 10741330
• 负责人: Luana Colloca
• 金额: $ 8.78万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2024-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10741330
• 关键词: Absence of pain sensation; Administrative Supplement; Affect; Age; Algorithms; Area; Behavioral; Biological; Biological Markers; Blood; Blood specimen; Candidate Disease Gene; Caring; Chronic; Classification; Clinical; Complex; Consensus; Data; Data Analyses; Dopamine; Endocannabinoids; Engineering; Ensure; Expectancy; Fostering; Funding; Future; Genes; Genetic; Genomics; Goals; Health; Individual; Interdisciplinary Study; Knowledge; Laboratories; Machine Learning; Medicine; Modeling; Molecular; Neural Pathways; Neurons; Opioid; Orofacial Pain; Pain; Pain intensity; Pain management; Participant; Pathway interactions; Patients; Phenotype; Placebo Effect; Placebos; Population; Predictive Factor; Preparation; Process; Prospective Studies; Proteomics; Psychological Factors; Publishing; Quality of life; Recommendation; Reporting; Research; Research Priority; Sampling; Serotonin; Severities; Severity of illness; Single Nucleotide Polymorphism; System; Temporomandibular Joint Disorders; Testing; Therapeutic; Twin Multiple Birth; United States National Academy of Sciences; Validation; Variant; Visual; Work; analog; chronic pain; chronic pain patient; chronic painful condition; clinical phenotype; clinically relevant; cohort; endophenotype; genetic variant; genome wide association study; machine learning model; molecular marker; non-opioid analgesic; orofacial; pain inhibition; pain reduction; pain score; pain signal; pill; precision medicine; psychologic; psychosocial; randomized, clinical trials; response; secondary analysis; sex; single-cell RNA sequencing; sociodemographics; trait; transcriptome; transcriptome sequencing; transcriptomic profiling; transcriptomics

This project in response to RFA-DE-22-011 aims to analyze existing data representing a subset of participants with Temporomandibular disorders (TMD) who underwent in-depth clinical, behavioral, and psychological phenotyping under R01 DE025946 (PI: Colloca, ending September 30, 2022). The proposed aims are substantially different from the original R01-work exploring genetic variants associated with expectancy-induced analgesia in chronic orofacial pain, psychological factors predicting placebo responders, and genes-related neuronal changes in the prefrontal and limbic areas associated with expectancy-induced analgesia. Using Dean’s Initiative Funds allocated to Dr. Colloca, we collected blood and extracted RNA-seq data from a subset of 74 TMD participants. With the behavioral, psychological, clinical and now, transcriptomic data from this subset of TMD participants, the central hypothesis is distinct Differently Expressed Genes (DEG) and pathways associated with Endogenous Pain Modulation (EPM) characterize those TMD participants who show the highest placebo effects. We will compare transcriptomic profiles associated with high versus low EPM via placebo effects tested in TMD participants (AIM1) and we will predict high EPM integrating transcriptomic, sociodemographic, clinical and psychological data (Exploratory Specific Aim 2) using machine learning models. In order to identify transcriptomic profiles of high placebo responsiveness, TMD participants will be divided into High Placebo Responders (HLR) and Low Placebo Responders (LPR) based on an average reported pain score cut-off of 30 on a visual analogue scale (VAS) anchored from zero=no pain to 100=maximum imaginable pain. Based on our prior published results, informative preliminary results, and DEG power calculation, we expect enough power to identify key DEG associations in HPR compared to those TMD who do not respond and/or have lower placebo responses while controlling for sex, age and pain severity. Importantly, unbiased enrichment analyses will be conducted to identify transcriptomic processes associated with EPM. Machine learning approaches (e.g., generalized boosted models) will allow us to integrate sociodemographic, clinical and psychological with transcriptomic markers to further characterize HPR in TMD participants. Our team is strong with complementary expertise, ensuring that this research will provide integrative models towards step- by-step discoveries of molecular mechanisms characterizing those who show the largest activation of EPM via placebo effects. This is the first project to use transcriptomic profiling and machine learning models to predict EPM in an understudied TMD population. Findings will have high clinical relevance and will inform more extensive studies generating knowledge that will be critical to guide future steps towards integrative and translational precision medicine.

该项目响应 RFA-DE-22-011 旨在分析代表参与者子集的现有数据 患有颞下颌关节紊乱病 (TMD) 的患者接受了深入的临床、行为和心理治疗 R01 DE025946 下的表型分析（PI：Colloca，于 2022 年 9 月 30 日结束）拟议的目标是 与探索与预期诱发相关的遗传变异的原始 R01 工作有很大不同 慢性口面部疼痛的镇痛、预测安慰剂反应者的心理因素以及基因相关 与期望引起的镇痛相关的前额叶和边缘区域的神经变化。 Dean’s Initiative Funds 分配给 Colloca 博士，我们收集了血液并从子集中提取了 RNA-seq 数据 74 名 TMD 参与者的行为、心理、临床和现在的转录组数据。 TMD 参与者的中心假设是不同的差异表达基因 (DEG) 和通路 与内源性疼痛调节 (EPM) 相关的 TMD 参与者表现出最高的特征 我们将通过安慰剂比较与高 EPM 和低 EPM 相关的转录组图谱。 在 TMD 参与者 (AIM1) 中测试了效果，我们将预测整合转录组的高 EPM， 使用机器学习的社会人口统计、临床和心理数据（探索性具体目标 2） 为了确定高安慰剂反应性的转录组特征，TMD 参与者将被 根据报告的平均值分为高安慰剂反应者 (HLR) 和低安慰剂反应者 (LPR) 视觉模拟评分 (VAS) 上的疼痛评分截止值为 30，从 0 = 无疼痛到 100 = 最大 基于我们之前发表的结果、信息丰富的初步结果和 DEG 功效。 通过计算，我们期望有足够的能力来识别 HPR 中关键的 DEG 关联，与那些 TMD 的人相比 在控制性别、年龄和疼痛严重程度时没有反应和/或安慰剂反应较低。 将进行无偏见的富集分析，以确定与 EPM 相关的转录组过程。 机器学习方法（例如广义增强模型）将使我们能够整合社会人口统计学、 我们的团队利用转录组标记来进一步表征 TMD 参与者的临床和心理特征。 具有强大的互补专业知识，这项研究将提供确保逐步迈向的整体模型 逐步发现 EPM 最大激活特征的分子机制 这是第一个使用转录组分析和机器学习模型来预测的项目。 EPM 在未充分研究的 TMD 人群中的研究结果将具有高度的临床相关性，并将提供更多信息。 广泛的研究产生的知识对于指导未来走向一体化和一体化至关重要 转化精准医学。

项目成果

The Nocebo Effect.

反安慰剂效应。

• 发表时间: 2024-01-23
• 作者: Colloca; Luana
• 通讯作者: Luana

Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain.

瑜伽和按摩与慢性口面部疼痛的小实验安慰剂效应有关。

• 发表时间: 2023-08
• 作者: Yin, Margaret;Muhammed, Salim A;Wang, Yang;Colloca, Luana
• 通讯作者: Colloca, Luana

Clinical Phenotypes Supporting the Relationship Between Sleep Disturbance and Impairment of Placebo Effects.

支持睡眠障碍与安慰剂效应受损之间关系的临床表型。

• 发表时间: 2024-03
• 作者: Wang, Yang;Varghese, Jeril;Muhammed, Salim;Lavigne, Gilles;Finan, Patrick;Colloca, Luana
• 通讯作者: Colloca, Luana

How negative and positive constructs and comorbid conditions contribute to disability in chronic orofacial pain.

消极和积极的结构以及合并症如何导致慢性口面部疼痛的残疾。

• 发表时间: 2023-01
• 作者: Thomas, Sharon;Wang, Yang;Cundiff;Massalee, Rachel;Colloca, Luana
• 通讯作者: Colloca, Luana

Predicting Treatment Responses in Patients With Osteoarthritis: Results From Two Phase III Tanezumab Randomized Clinical Trials.

预测骨关节炎患者的治疗反应：两项 III 期 Tanezumab 随机临床试验的结果。

• 发表时间: 2023-04
• 影响因子: 6.7
• 作者: Colloca, Luana;Dworkin, Robert H;Farrar, John T;Tive, Leslie;Yang, Jiyue;Viktrup, Lars;Dasic, Gorana;West, Christine R;Whalen, Ed;Brown, Mark T;Gilbert, Steven A;Verburg, Kenneth M
• 通讯作者: Verburg, Kenneth M