Dynamic Evaluation of Neural Mechanisms for Affective Touch: Pathways for Touch-induced Pleasantness and Pain Modulation

情感触摸神经机制的动态评估：触摸引起的愉悦感和疼痛调节的途径

• 批准号: 10660199
• 负责人: Laura K Case
• 金额: $ 69.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660199
• 关键词: Ablation; Address; Adult; Affective; Afferent Pathways; Amyloid beta-Protein; Anterior; Anterolateral; Area; Brain; Brain imaging; C Fiber; Central Nervous System; Clinical; Complementary therapies; Complex; Cordotomy; Data; Deafferentation procedure; Dedications; Dependence; Disease; Esthesia; Evaluation; Fiber; Functional Magnetic Resonance Imaging; Goals; Health; Impairment; Individual; Individual Differences; Insula of Reil; Interneurons; Left; Light; Local Anesthetics; Machine Learning; Manipulative Therapies; Maps; Massage; Measures; Methods; Mind-Body Intervention; Mission; National Center for Complementary and Integrative Health; Nerve Fibers; Nerve compression syndrome; Neural Pathways; Nociceptors; Outcome; Pain; Pain management; Parasympathetic Nervous System; Pathway interactions; Patients; Peripheral; Process; Public Health; Relaxation; Relaxation Therapy; Research; Research Personnel; Role; Signal Transduction; Skin; Somatosensory Cortex; Spinal; Strategic Planning; Stroke; Study Subject; Tactile; Temperature Sense; Testing; Time; Touch sensation; Vertebral column; chronic pain; cingulate cortex; heart rate variability; individual response; innovation; mechanotransduction; neuromechanism; neuroregulation; novel; pain reduction; pain relief; predictive modeling; preference; preservation; pressure; response; secondary outcome; theories; tool; volunteer

Project Summary/Abstract The exact mechanisms by which light stroking and deep pressure – components of massage therapy – induce pleasantness and pain modulation are not understood. Given the frequent use of massage therapy for relaxation and pain relief, and the need for complementary tools for chronic pain, there is a critical need to study the mechanisms of specific forms of affective touch. Our long-term goal is to elucidate the mechanisms by which manual therapies induce pleasant relaxation and pain relief. Our overall objectives in this application are to (1) Determine the extent to which A- and C-fibers contribute to affective effects of gentle stroking, 2) Determine the extent to which A- and C-fibers contribute to affective effects of deep pressure, and 3) Determine the contribution of C-fibers to neural mechanisms of touch-induced pleasantness and pain modulation. We will also (Exploratory) use machine learning to identify individual contributions of C-tactile (CT) fibers to neural mechanisms of touch pleasantness and pain modulation, and the association of interoceptive sensibility with CT effects. Our central hypothesis is that A-fibers are necessary but not sufficient for the pleasantness of gentle stroking and unnecessary for its pain reduction, but are necessary and sufficient for the pleasantness and pain reduction of deep pressure. Further, we hypothesize that left anterior insula and anterior cingulate cortex activation will predict CT contributions to modulation of pain by touch. We will conduct a two session within-subject study in healthy adult volunteers to test the effects of A- and C-fiber blockade on the pleasantness and pain modulation induced by slow stroking (N = 24) and deep pressure (N = 24). We will then test effects of A-fiber blockade on brain mechanisms of pain modulation during fMRI, and relationships between CT contributions and touch pleasantness, pain modulation, and interoceptive sensibility (N = 36). Effects of CT inputs on heart rate variability will comprise a secondary outcome. Upon successful completion of the proposed research, we expect to have identified the role of A- and C-fibers in the pathways and major effects of affective touch. This contribution is expected to be significant because it will define the pathways for two major forms of affective touch and their effects on pain, providing reliable information about non-invasive measures for pain control and potential targets for noninvasive neuromodulation of pain. Further, this project is innovative because it explores a novel affective touch pathway, applies a novel method to causally test afferent pathways for affective touch, and uses machine learning to explore individual differences in the contributions of CTs to neural mechanisms for affective touch. Our proposed project seeks to elucidate pathways for two major forms of affective touch commonly engaged by massage. This research will have a positive impact by opening new horizons for mechanistic research on effects of touch in health and disease, and may provide targets for neuromodulation in the treatment of pain.

项目摘要/摘要 轻抚触和深按压--按摩疗法的组成部分--诱导的确切机制 愉悦和痛苦的调制方式是不被理解的。由于经常使用按摩疗法来放松 和疼痛缓解，以及治疗慢性疼痛的辅助工具的需要，迫切需要研究 特定形式的情感触摸的机制。我们的长期目标是阐明 徒手疗法能带来愉悦的放松和疼痛缓解。我们在此应用程序中的总体目标是(1) 确定A和C纤维对温柔中风的情感效果的贡献程度，2)确定 A和C纤维对深度压力的情感效应的贡献程度，以及3)决定贡献 C纤维与触摸诱导的愉悦和疼痛调制的神经机制有关。我们还将(探索性) 使用机器学习来识别C-触觉(CT)纤维对触摸神经机制的个体贡献 愉悦感和疼痛调节，以及感觉间敏感性与CT效应的关联。我们的中央 假设A-纤维是温柔抚摸和舒缓抚摸的必要条件，但不是充分条件。 对于它的疼痛减轻是不必要的，但对于快乐和减轻疼痛是必要的和充分的 深部压力。此外，我们假设左侧前岛叶和前扣带回皮质的激活将预测 CT对触觉痛觉调制的贡献。我们将在健康的基础上进行两次主题内研究 成年志愿者测试A、C纤维阻断对快感和痛觉调制的影响 缓慢卒中(N=24)和深部加压(N=24)。然后我们将测试A纤维阻断对大脑的影响 FMRI中痛觉调制的机制以及CT贡献与触摸的关系 愉悦感、痛觉调制和内感敏感性(N=36)。CT输入对心率变异性的影响 将包括一个次要的结果。在成功完成拟议的研究后，我们预计将有 确定了A和C纤维在情感触摸的通路和主要影响中的作用。这一贡献是 预计将具有重大意义，因为它将定义两种主要形式的情感触摸的途径，以及它们的 对疼痛的影响，提供关于非侵入性疼痛控制措施和潜在靶点的可靠信息 对疼痛进行非侵入性神经调节。此外，这个项目具有创新性，因为它探索了一种新颖的情感 触摸路径，应用一种新的方法对传入路径进行情感触摸的因果测试，并使用机器 学习探索CTs对情感触摸神经机制的贡献的个体差异。 我们建议的项目旨在阐明两种主要形式的情感触摸的途径 按摩。这项研究将为效应的机理研究开辟新的视野，将产生积极的影响 触摸在健康和疾病中的作用，并可能为治疗疼痛的神经调节提供靶点。