Integrating brain and behavioral measures of central pain inhibition to personalize treatment in chronic pain management

整合中枢疼痛抑制的大脑和行为测量，以实现慢性疼痛管理的个性化治疗

• 批准号: 10448932
• 负责人: Benedict J Alter
• 金额: $ 18.92万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448932
• 关键词: Absence of pain sensation; Acute Pain; Address; Affect; Analgesics; Animal Model; Behavioral; Behavioral Paradigm; Blinded; Brain; Brain imaging; Chronic; Clinic; Clinical; Clinical Research; Clinical Trials; Complement; Cross-Sectional Studies; Data; Diabetes Mellitus; Distant; Drops; Evaluation; Functional disorder; Future; Goals; Hand; Heart Diseases; Heterogeneity; Human; Imaging Device; Immersion; Impairment; Injury; K-Series Research Career Programs; Knee; Knee Osteoarthritis; Knowledge; Malignant Neoplasms; Measurement; Measures; Medial; Mentors; Meta-Analysis; Modeling; Neuraxis; Neurosciences Research; Pain; Pain Threshold; Pain intensity; Pain management; Pain-Free; Patient Care; Patient-Focused Outcomes; Patients; Phenotype; Physicians; Physiological; Population; Positioning Attribute; Prediction of Response to Therapy; Prefrontal Cortex; Randomized Controlled Trials; Recording of previous events; Reproducibility; Research; Role; Scientist; Sensory; Severities; Signal Transduction; Site; Stimulus; Subgroup; Syndrome; Testing; Time; Training; Translational Research; United States; Universities; Walking; Water; Work; arthritic pain; base; behavior measurement; career; central pain; chronic neuropathic pain; chronic pain; chronic pain management; chronic pain patient; chronic painful condition; clinical pain; cohort; conditioned pain modulation; conditioning; cost; cost effective; distraction; duloxetine; functional near infrared spectroscopy; healthy volunteer; heat stimulus; hemodynamics; improved; joint destruction; knee pain; knowledgebase; meetings; neural correlate; neuroimaging; novel; osteoarthritis pain; pain inhibition; pain relief; patient oriented research; patient population; patient subsets; personalized care; personalized medicine; preclinical study; predicting response; predictive marker; pressure; prevent; programs; prospective; response; secondary analysis; skills; somatosensory; tool; treatment effect; treatment response; volunteer

Although pain inhibition by the central nervous system (CNS) strongly modulates acute pain in the lab, its relevance for patient outcomes is less well known. Studies with animal models, human behavioral paradigms, and neuroimaging have implicated central pain inhibition in the pathophysiology of chronic pain. However, the most commonly used assessments of central pain inhibition in patients are limited by technical aspects, expense, and accessibility, preventing their widespread use and resulting in a knowledge gap in how central pain inhibition impacts patient outcomes and treatment response. The goal of the current project is to define changes in central pain inhibition in patients with chronic pain using novel brain and behavioral tools, including functional near-infrared spectroscopy (fNIRS) and offset analgesia. FNIRS allows cost-effective measurement of activity-dependent cortical hemodynamic changes in an ambulatory, clinic based setting. Offset analgesia, defined as a reduction in subjective pain intensity if a noxious stimulus is preceded by a stronger stimulus, is mechanistically distinct from the most commonly used measure of central pain inhibition, conditioned pain modulation. The central hypothesis is that offset analgesia is impaired and its neural correlates altered in patients with chronic pain. Additionally, we hypothesize that greater loss of central pain inhibition at baseline is associated with greater pain relief with duloxetine, which may rescue deficient pain inhibition. The proposal rationale is that measures of pain inhibition will identify subgroups of patients which will improve future RCTs by focusing studies on phenotypically-distinct populations and, ultimately, improving patient care by personalizing pain treatment. In this career development award, three aims are proposed. First, the relationship of offset analgesia and chronic pain intensity will be evaluated in a cross-sectional study comparing offset analgesia magnitude across patients with high or low chronic knee pain intensity but the same degree of joint degeneration. Second, in this same study, fNIRS will be used to define cortical correlates of offset analgesia, extending the applicant’s preliminary data in young, healthy volunteers. Third, a prospective trial will be performed in patients with chronic knee pain as a first step in investigating the impact of pain inhibition on treatment response to duloxetine. These studies provide hands-on training for the applicant in developing research skills related to brain imaging and clinical trials and will be complemented by mentoring and evaluation meetings, formal didactics coursework, seminars, and meetings. The project will be conducted at the University of Pittsburgh, which has outstanding support for clinical and translational research and a long history of developing independent physician-scientists. Together, this project will position the applicant well to achieve independence in chronic pain patient-oriented research and allow subsequent studies rigorously examining central pain inhibition as a predictive biomarker of treatment response.

尽管中枢神经系统（CNS）抑制疼痛，强烈调节实验室的急性疼痛，但ISS 与动物模型，人类行为范式的研究相关性。 神经影像学已暗示了慢性疼痛的病理生理学中心疼痛抑制。 最常见的是患者中心疼痛抑制的usesssmessmessmess受到技术方面的限制， 费用和可访问性，防止广泛使用并导致知识差距 疼痛抑制作用会影响患者的预后和治疗反应。 使用Paing paing paing paing新工具，包括 功能性近红外光谱（FNIRS）和抵消镇痛。 依赖活性的皮质血流动力学的基于诊所的镇痛。 定义为减少主观疼痛强度的降低 机械学上与最常用的中枢疼痛抑制，条件疼痛的量度不同 模块的中心假设是，止痛 慢性疼痛的患者。 与杜洛西汀缓解疼痛相关，这可能会救出疼痛感染疼痛。 理由是，疼痛居民的介绍将确定患者的亚组，这将改善未来的RCT 通过将研究重点放在表型赋予的普及，并最终通过By by by By By By By By By By By By By By By By By By By By By By By By By By By By By By By By B BY BY CARACH CARACH进行。 在这个Carere Development奖中，提出了三个目标 在横截面研究中，将评估止痛镇痛和慢性疼痛强度的关系 比较慢性膝关节疼痛强度或低的患者（但较低）的镇痛幅度。 相同程度的关节变性。 镇痛，在年轻，健康的志愿者中扩展了申请人的初步数据 前瞻性试验将通过长期膝盖疼痛的患者进行，因为第一步调查了影响的影响 对杜洛西汀的治疗反应抑制作用。 在开发与大脑成像和临床试验有关的研究技能时，将通过指导来补充 和评估会议，正式的教学课程，研讨会和会议。 在匹兹堡大学（University of Pittsburgh 发展独立医师科学家的历史。 实现慢性患者研究的独立性，并允许严格的研究 将中心疼痛抑制作用作为信任反应的预测生物标志物。