Identifying neuromodulation targets for pain in the human brain

识别人脑疼痛的神经调节目标

• 批准号: 10450987
• 负责人: MICHAEL D FOX
• 金额: $ 26.85万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450987
• 关键词: Adverse effects; Analgesics; Atlases; Base of the Brain; Brain; Brain hemorrhage; Brain region; Clinical Trials; Data; Data Set; Databases; Dependence; Development; Dystonia; Enrollment; Foxes; Future; Human; Ischemic Stroke; Lesion; Link; Literature; Location; Magnetic Resonance Imaging; Maps; Mental Depression; Mental disorders; Metabolism; Methods; Motor Cortex; Neuroanatomy; Neurologic; Neurologic Symptoms; Pain; Pain Map; Pain management; Parkinson Disease; Patients; Pharmacology; Quality of life; Questionnaires; Reporting; Rest; Symptoms; Testing; Thalamic structure; Transcranial magnetic stimulation; Tremor; addiction; base; central pain; clinically significant; cohort; fluorodeoxyglucose positron emission tomography; improved; metabolic imaging; nervous system disorder; neuroimaging; neuropsychiatric symptom; neuroregulation; novel strategies; pain relief; painful neuropathy; post stroke; post stroke pain; prospective; psychiatric symptom; side effect; stroke outcome; thalamic pain; therapeutic target

Identifying neuromodulation targets for pain in the human brain Neuropathic pain is prevalent across many different neurological and psychiatric disorders and has one of the largest adverse effects on quality of life. Pharmacological pain treatments often have limited efficacy and undesirable side effects, including dependence and addiction. Neuromodulation treatments such as transcranial magnetic stimulation show promise for pain while avoiding the side effects associated with pain medications. An obstacle to improving neuromodulation treatment is identifying the human brain regions responsible for pain. Traditional functional neuroimaging studies only identify correlates of pain which could be causing symptoms, compensating for symptoms, or simply serving as a marker of symptoms. This ambiguity is a problem when seeking to identify therapeutic targets. Unlike functional neuroimaging, lesion studies allow for casual links between symptoms and human neuroanatomy. The PI has developed and validated a new method to identify neuromodulation targets in the human brain based on brain lesions and a map of human brain connectivity. Called lesion network mapping, this approach has been used to map numerous neurological and psychiatric symptoms to brain networks (Fox 2018, NEJM). Brain networks identified using this approach have proven to be effective neuromodulation targets for symptoms such as tremor, Parkinson’s disease, dystonia, and depression. Our preliminary data suggests this method is equally valuable for mapping pain, including identification of therapeutic targets. Here, we will use this approach to map pain to a human brain circuit based on lesion locations previously reported to cause pain (Aim 1), a dedicated dataset focused on thalamic lesions causing or not causing pain (Aim 2), and a prospective dataset of patients longitudinally assessed for development of post-stroke pain (Aim 3). We hypothesize that; (1) lesions causing pain will map to a common brain network; (2) this network will show abnormal metabolism in patients with post stroke pain, (3) this network will predict who will develop post-stroke pain; and (4) this pain network will include primary motor cortex, our best validated neuromodulation target for pain. Completion of these aims will identify a candidate human brain network causally linked to pain. Once identified, this network can be validated in future trials with more detailed characterization of post stroke pain and used as an improved target for neuromodulation that can be tested in clinical trials.

确定人脑中疼痛的神经调节靶点 神经病理性疼痛在许多不同的神经和精神障碍中普遍存在，并具有 对生活质量的最大不利影响。药物治疗疼痛的效果往往有限，而且 不良副作用，包括依赖和上瘾。神经调节治疗，如经颅 磁刺激显示出止痛的前景，同时避免了与止痛药相关的副作用。一个 改善神经调节治疗的障碍是确定人类大脑中负责疼痛的区域。 传统的功能神经成像研究只确定可能导致症状的疼痛的相关性， 补偿症状，或简单地作为症状的标志。这种模棱两可是一个问题，当 寻求确定治疗靶点。与功能神经成像不同，病变研究允许随意联系 症状和人类神经解剖学之间的关系。PI已经开发并验证了一种新的识别方法 基于大脑损伤和人脑连通性地图的人脑神经调节目标。 这种方法被称为病变网络映射，已经被用于绘制许多神经学和精神病学的地图 症状到大脑网络(福克斯2018，NEJM)。使用这种方法识别的大脑网络已被证明 成为治疗震颤、帕金森氏症、肌张力障碍等症状的有效神经调节靶点 抑郁症。我们的初步数据表明，这种方法在绘制疼痛地图方面同样有价值，包括 确定治疗靶点。在这里，我们将使用这种方法将疼痛映射到人类大脑的一个基于 关于先前报告的引起疼痛的病变位置(AIM 1)，这是一个专注于丘脑病变的专用数据集 引起或不引起疼痛(目标2)，以及纵向评估的患者的预期数据集 中风后疼痛的发展(目标3)。我们假设：(1)引起疼痛的损伤将映射到共同的 大脑网络；(2)这个网络会显示中风后疼痛患者的代谢异常，(3)这个网络 将预测谁会出现中风后疼痛；以及(4)这个疼痛网络将包括初级运动皮质，我们的 最有效的疼痛神经调节靶点。完成这些目标将确定一个候选的人脑 网络与痛苦有着因果关系。一旦确定，此网络可以在未来的试验中进行验证，并提供更详细的信息 卒中后疼痛的特征，并用作神经调节的改进靶点，可在 临床试验。