High resolution interrogation of the insula in mechanisms of chronic pain

慢性疼痛机制中岛叶的高分辨率询问

• 批准号: 10575673
• 负责人: Wynn Legon
• 金额: $ 22.89万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-22 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10575673
• 关键词: Acute; Affect; American; Anterior; Behavior; Brain; Central Nervous System; Cephalic; Characteristics; Clinical; Data; Economics; Effectiveness; Electric Stimulation; Epidemic; Evoked Potentials; Feeling; Fibromyalgia; Focused Ultrasound; Functional disorder; Goals; Health; Human; Human Volunteers; Hyperalgesia; Individual; Insula of Reil; Lasers; Link; Measures; Mental Depression; Methods; Neurosurgical Procedures; Opioid; Pain; Pain management; Penetration; Pharmacological Treatment; Public Health; Reporting; Resolution; Role; Safety; Sensory; Source; Spottings; Stimulus; Surface; Syndrome; Techniques; Testing; Transcranial magnetic stimulation; Translations; United States; addiction; allodynia; autism spectrum disorder; behavior measurement; central pain; central sensitization; chronic pain; chronic pain management; chronic painful condition; conditioned pain modulation; cost; cranium; effective therapy; effectiveness testing; experience; fibromyalgia patients; millimeter; neuroregulation; noninvasive brain stimulation; novel; pain processing; response; sensory gating; sensory input; sensory system; social; stem; tool; ultrasound

ABSTRACT Chronic pain is a major public health problem. An estimated 100 million Americans have experienced chronic pain producing significant economic and social burden. Pharmacological treatments frequently require the use of opioids resulting in a major epidemic of abuse in the United States. New, non-addicting treatments for pain are critically needed. Neuromodulation with low intensity focused ultrasound (LIFU) may provide a non- pharmacological treatment for chronic pain. The enormous potential of LIFU stems from the ability to focus ultrasound through the intact skull to a millimeter-sized focal spot size anywhere in the brain. One promising target to treat chronic pain is the insular cortex. Multiple lines of evidence support the involvement of the insula in abnormal pain modulation or central sensitization and pain chronicity. Unfortunately, the insula lies deep to the cortex and contains small discrete sub-regions making non-invasive access difficult. Preliminary data demonstrates that LIFU can target individual sub-regions of the insula non-invasively to inhibit laser-evoked potentials as well as reduce subjective report of pain in humans. It is the purpose of this proposal to investigate the causal influence of LIFU to sub-regions of the insula on brain activity and behavior related to central sensitization in healthy human volunteers and fibromyalgia patients. This is important as central sensitization is a shared characteristic of many chronic pain conditions. It is the long-term goal of this project to advance LIFU as a human pain management tool to enhance the health and reduce suffering in those with chronic pain.

摘要 慢性疼痛是一个主要的公共卫生问题。据估计，有1亿美国人患有慢性 造成巨大的经济和社会负担。药物治疗经常需要使用 阿片类药物的滥用在美国造成了严重的流行病。新的，非成瘾性的疼痛治疗 是非常需要的。使用低强度聚焦超声（LIFU）的神经调节可以提供非- 用于慢性疼痛的药物治疗。LIFU的巨大潜力源于其专注于 超声波穿过完整的头骨，在大脑的任何地方形成毫米大小的焦点。一个有希望 治疗慢性疼痛的目标是岛叶皮层。多条证据都支持 异常疼痛调节或中枢敏感化和疼痛慢性化。不幸的是， 并且包含小的离散子区域，使得非侵入性进入困难。初步数据 表明LIFU可以非侵入性地靶向视网膜的单个亚区域，以抑制激光诱发的 潜在的，以及减少主观报告的疼痛在人类。本提案的目的是调查 LIFU对大脑皮层亚区域对与中枢神经系统相关的大脑活动和行为的因果影响 在健康人类志愿者和纤维肌痛患者中的致敏性。这一点很重要，因为中枢敏感化是 这是许多慢性疼痛症状的共同特征。本项目的长期目标是推进LIFU 作为人类疼痛管理工具，以增强健康和减少慢性疼痛患者的痛苦。