In-vivo Assessment of Neuroinflammation in Painful Trigeminal Neuropathy

疼痛三叉神经病神经炎症的体内评估

• 批准号: 10674197
• 负责人: Hsinlin Thomas Cheng
• 金额: $ 21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674197
• 关键词: Affect; Anterior; Anti-Inflammatory Agents; Area; Astrocytes; Behavioral; Brain; Brain Stem; Brain imaging; Brain scan; Central Nervous System; Chronic low back pain; Clinical; Contralateral; Data; Data Set; Development; Disease; Disease Management; Enrollment; Etiology; Face; Facial Pain; Fibromyalgia; Generations; HIV; Human; Image; Imaging technology; Inflammatory; Intervention; Investigation; Ipsilateral; Knee Osteoarthritis; Knowledge; Low Back Pain; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Measures; Medical; Methodology; Microglia; Migraine; Molecular; Multimodal Imaging; Neurodegenerative Disorders; Neuroglia; Neurologist; Neurons; Nociception; Operative Surgical Procedures; Oral; Pain; Pain Disorder; Pain management; Participant; Pathway interactions; Patient Schedules; Patient imaging; Patients; Peripheral; Persistent pain; Positioning Attribute; Positron-Emission Tomography; Prediction of Response to Therapy; Prednisone; Proteins; Questionnaires; Rest; Role; Scanning; Schedule; Sensory; Severities; Side; Signal Transduction; Somatosensory Cortex; Spatial Distribution; Specificity; Steroid therapy; Steroids; Structure of trigeminal ganglion; Symptoms; Testing; Thalamic structure; Translations; Trauma; Trigeminal Nerve Diseases; Trigeminal System; Trigeminal nerve structure; Virus Diseases; Visit; Work; cell type; chronic pain; chronic pain patient; chronic painful condition; cingulate cortex; clinically significant; depressive symptoms; experience; glial activation; imaging study; improved; in vivo; multimodality; myoinositol; neural; neuroinflammation; novel; overexpression; pain-related disability; painful neuropathy; pre-clinical; preclinical study; predicting response; prevent; radioligand; recruit; somatosensory; therapeutic target; tool

Painful trigeminal neuropathy (PTN) is defined as facial pain in the distribution(s) of one or more branches of the trigeminal nerve, associated with neural damage induced by trauma, viral infection, or other causes. PTN is very unresponsive to medical and surgical treatments. Clearly, a more in-depth knowledge of the molecular pathomechanisms of PTN are in urgent need to improve the management of this disorder. In the last six years our group has demonstrated the presence of increased levels of the 18kDa translocator protein (TSPO, using positron emission tomography) and/or myo-inositol (mIns, using magnetic resonance spectroscopy), in the brains of patients with various chronic pain conditions. Because both TSPO and mIns are overexpressed by glial cells, our results suggest that neuroinflammation might be a pervasive phenomenon that can be observed across multiple, etiologically heterogeneous human pain disorders, but in a disorder-specific spatial distribution within the central nervous system. Despite these advances, the clinical significance of these brain inflammatory signals (e.g., whether neuroinflammation imaging could be used to identify patients more likely to respond to anti-inflammatory therapies) remains to be evaluated. In this exploratory project, we will recruit PTN patients scheduled to receive oral steroid therapy. All participants will be evaluated clinically by an experienced neurologist and, prior to commencing their treatment, receive brain imaging with integrated (i.e., simultaneous) positron emission tomography / magnetic resonance imaging (PET/MRI) and [11C]PBR28, a second-generation radioligand for TSPO, which we have used to demonstrate glial activation in patients with pain or neurodegenerative disorders. After the scan, participants will undergo a 3-week treatment with the steroid prednisone, followed by another clinical/behavioral visit. Clinical characterization will include quantitative sensory testing and questionnaires. Patients’ imaging data will be compared to an existing dataset of healthy controls and chronic pain patients with a different etiology (chronic low back pain) to assess the specificity of our findings to PTN. For Aim 1, we will assess in-vivo neuroinflammation in painful trigeminal neuropathy, using multimodal brain imaging. For Aim 2 we will test the brain neuroinflammatory signals’ ability to predict response to steroid treatment. This work will advance our understanding of the clinical significance of neuroinflammation in chronic pain conditions. While this project is focused on neuropathic pain, identifying the role of glia in the development and maintenance of persistent neuropathic pain and pain-related disability in humans will have important practical implications for the management of a wide range of pain disorders. For instance, it will provide crucial human evidence contributing to rationale for the development of tailored interventions focused on glial modulation.

疼痛性三叉神经病变（PTN）定义为面部疼痛的一个或多个分布， 三叉神经分支，与创伤、病毒感染或其他引起的神经损伤有关 可使. PTN对药物和手术治疗非常无反应。显然，更深入地了解 PTN的分子病理机制是迫切需要的，以改善这种疾病的管理。 在过去的六年里，我们的小组已经证明了18 kDa水平增加的存在。 转运蛋白（TSPO，使用正电子发射断层扫描）和/或肌醇（mIns，使用磁共振成像） 共振光谱学），在具有各种慢性疼痛状况的患者的大脑中。因为TSPO 和mIns由胶质细胞过度表达，我们的结果表明神经炎症可能是一个普遍的， 这一现象可以在多种病因异质性人类疼痛障碍中观察到，但在一个 中枢神经系统内的疾病特异性空间分布。尽管取得了这些进展，临床上 这些脑炎症信号的意义（例如，神经炎症成像是否可以用于 确定更可能对抗炎治疗有反应的患者）仍有待评估。 在这个探索性项目中，我们将招募计划接受口服类固醇治疗的PTN患者。所有 参与者将由有经验的神经科医生进行临床评估，在开始治疗之前， 接收具有集成的脑成像（即，正电子发射断层扫描/磁共振 成像（PET/MRI）和[11 C] PBR 28，TSPO的第二代放射性配体，我们已经使用它来 在患有疼痛或神经退行性疾病的患者中证实神经胶质活化。扫描后，参与者 将接受为期3周的类固醇泼尼松治疗，随后进行另一次临床/行为访视。 临床表征将包括定量感觉测试和问卷调查。患者的成像数据将 与现有的健康对照组和具有不同病因的慢性疼痛患者数据集进行比较 （慢性腰痛）来评估我们的研究结果对PTN的特异性。 对于目标1，我们将评估疼痛性三叉神经病变的体内神经炎症，使用多模式 脑成像对于目标2，我们将测试大脑神经炎症信号预测类固醇反应的能力 治疗这项工作将促进我们对慢性神经炎性疾病的临床意义的理解。 疼痛状况。 虽然这个项目的重点是神经性疼痛，确定神经胶质细胞在发展中的作用， 在人类中维持持续的神经性疼痛和疼痛相关的残疾将具有重要的实际意义。 对广泛的疼痛障碍的管理的影响。例如，它将提供关键的人类 证据有助于开发针对神经胶质调节的定制干预措施的合理性。