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 (PTN) 被定义为一种或多种分布的面部疼痛 三叉神经的分支，与外伤、病毒感染或其他引起的神经损伤有关 原因。 PTN 对药物和手术治疗的反应非常迟钝。可见，对知识的了解更加深入 PTN 的分子病理机制迫切需要改善这种疾病的治疗。 在过去的六年中，我们的团队证明了 18kDa 水平的增加 易位蛋白（TSPO，使用正电子发射断层扫描）和/或肌醇（mIns，使用磁 共振光谱），在患有各种慢性疼痛的患者的大脑中。因为 TSPO 和 mIns 被神经胶质细胞过度表达，我们的结果表明神经炎症可能是一种普遍的 这种现象可以在多种不同病因的人类疼痛疾病中观察到，但在 中枢神经系统内疾病特异性的空间分布。尽管取得了这些进展，临床 这些大脑炎症信号的重要性（例如，神经炎症成像是否可用于 确定更有可能对抗炎治疗产生反应的患者）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。全部 参与者将由经验丰富的神经科医生进行临床评估，并且在开始治疗之前， 通过集成（即同时）正电子发射断层扫描/磁共振接收脑部成像 成像 (PET/MRI) 和 [11C]PBR28，一种用于 TSPO 的第二代放射性配体，我们已将其用于 证明患有疼痛或神经退行性疾病的患者的神经胶质细胞激活。扫描结束后，参与者 将接受为期 3 周的类固醇泼尼松治疗，然后进行另一次临床/行为访视。 临床表征将包括定量感官测试和问卷调查。患者的影像数据将 与健康对照和具有不同病因的慢性疼痛患者的现有数据集进行比较 （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，我们将使用多模式评估疼痛性三叉神经病的体内神经炎症 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。这项工作将增进我们对慢性炎症中神经炎症的临床意义的理解。 疼痛情况。 虽然该项目的重点是神经性疼痛，但确定了神经胶质细胞在发育和神经病理性疼痛中的作用。 维持人类持续性神经性疼痛和疼痛相关的残疾将具有重要的实际意义 对治疗多种疼痛疾病的影响。例如，它将提供至关重要的人力 证据有助于制定针对神经胶质调节的定制干预措施的理由。