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

项目概要/摘要 按摩疗法的组成部分--轻轻抚摸和深压--诱导 愉悦和疼痛调节还不清楚。由于经常使用按摩疗法放松 和缓解疼痛，以及对慢性疼痛的补充工具的需求，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 手工疗法引起愉快的放松和疼痛缓解。我们在本申请中的总体目标是（1） 确定A-和C-纤维对轻轻抚摸的情感影响的程度，2）确定 A-和C-纤维对深层压力的情感效应的贡献程度，以及3）确定贡献 C-纤维的神经机制的触摸引起的愉快和疼痛调制。我们也将（探索性） 使用机器学习来识别C-触觉（CT）纤维对触觉神经机制的个体贡献 愉悦和疼痛调制，以及内感受性与CT效应的相关性。我们的中央 假设是A纤维是必要的，但不足以使温柔的抚摸感到愉快， 不必要的疼痛减少，但必要的和足够的愉快和疼痛减少 深层压力此外，我们假设左前扣带回和前扣带皮层激活将预测 CT对触摸疼痛调制的贡献。我们将在健康受试者中进行两个阶段的受试者内研究 成年志愿者测试A-和C-纤维阻断对诱发的愉悦和疼痛调制的影响。 慢拍（N = 24）和深压（N = 24）。然后我们将测试A纤维阻断对大脑的影响， 在功能磁共振成像过程中的疼痛调制机制，以及CT贡献和触摸之间的关系 愉悦、疼痛调节和内感受性敏感性（N = 36）。CT输入对心率变异性的影响 将包含次要结局。在建议的研究成功完成后，我们预计 确定了A和C纤维在情感触摸的途径和主要影响中的作用。这种贡献 预计将是重要的，因为它将定义两种主要形式的情感触摸和他们的路径。 对疼痛的影响，提供关于疼痛控制和潜在靶点的非侵入性措施的可靠信息 非侵入性神经调节疼痛此外，这个项目是创新的，因为它探索了一种新的情感 触觉通路，应用一种新的方法来因果测试情感触摸的传入通路，并使用机器 学习探索CT对情感触摸神经机制的贡献的个体差异。 我们提出的项目旨在阐明两种主要形式的情感触摸的途径， 按摩这项研究将通过为效应的机理研究开辟新的视野而产生积极的影响 触摸在健康和疾病中的作用，并可能为疼痛治疗中的神经调节提供目标。

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.