The role of neuroinflammation in human peripheral neuropathic pain

神经炎症在人类周围神经病理性疼痛中的作用

• 批准号: 10366539
• 负责人: Marco Luciano Loggia
• 金额: $ 73.36万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366539
• 关键词: Accounting; Adult; Astrocytes; Behavioral; Boston; Brain; Brain imaging; Carpal Tunnel Syndrome; Cervical spinal cord structure; Clinical; Coupled; Data; Development; Digit structure; Etiology; Evaluation; Exhibits; Finger Agnosias; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Hand; Human; Image; Intervention; Link; Magnetic Resonance Imaging; Maintenance; Measures; Microglia; Motor; Nerve Degeneration; Nerve compression syndrome; Neural Conduction; Neuraxis; Neurodegenerative Disorders; Neuroglia; Neuroimmune; Neuronal Plasticity; Neuropathy; Operative Surgical Procedures; Outcome; Pain; Pain Disorder; Pain-Free; Paresthesia; Participant; Pathway interactions; Patients; Performance; Peripheral; Peripheral Nerves; Positron-Emission Tomography; Pre-Clinical Model; Proteins; Psychomotor Performance; Questionnaires; Radial; Role; Scanning; Self Administration; Sensory; Severities; Signal Transduction; Signs and Symptoms; Somatosensory Cortex; Spinal Cord; Symptoms; Testing; Thalamic structure; Time; Wrist; afferent nerve; chronic pain; chronic pain patient; clinical pain; clinically significant; dermatome; glial activation; healthy volunteer; irritation; median nerve; nerve supply; neuroinflammation; neurophysiology; pain outcome; pain-related disability; painful neuropathy; predicting response; radioligand; response; sensory discrimination; somatosensory; spinal cord imaging; volunteer

In this proposal, we will investigate the role of neuroinflammation in neuropathic pain by evaluating patients suffering from a common entrapment neuropathy, carpal tunnel syndrome (CTS). We will clinically evaluate and then scan a total of 100 participants: 80 patients suffering from CTS and 20 healthy volunteers. All participants will be evaluated clinically, and receive brain and spinal cord imaging with integrated Positron Emission Tomography / Magnetic Resonance (PET/MR) imaging and [11C]PBR28, a second-generation radioligand for the 18 kDa translocator protein (TSPO), which we have previously used to demonstrate glial activation in chronic pain patients and neurodegenerative disorders. Patients will be re-scanned and evaluated clinically a second time, after carpal tunnel release surgery. The first Aim is to investigate the presence of neuroinflammation in CTS patients. We hypothesize that, compared to healthy adults, CTS patients will demonstrate higher [11C]PBR28 PET signal in the brain (thalamus and the hand representation of the primary somatosensory cortex, S1) and in the lower cervical spinal cord (corresponding to the territory of innervation of the median nerve in dermatomes C6-C7). We further hypothesize that higher brain/cord [11C]PBR28 PET signal will be associated with higher clinical pain, increased median nerve conduction latency, more severe functional deficits (i.e., worse finger agnosia and fine motor performance) and more severe neuroplastic changes (i.e., a smaller separation between S1 cortical representations for digits 2 and 3). The second Aim is to assess the effect of surgery on neuroinflammation and neuroplastic alterations in CTS patients. We hypothesize that 3 months after surgery, CTS patients will, on average, demonstrate reduced brain/cord [11C]PBR28 PET signal and increased D2/D3 S1 separation, compared to before the surgery. We also hypothesize that these brain changes will be correlated with each other, and with the reduction in pain and functional deficits. The final Aim is to evaluate neuroinflammation and neuroplastic alterations as predictors of response to surgery. We hypothesize that higher pre-surgical brain/cord [11C]PBR28 PET signal and reduced D2/D3 S1 separation will predict poorer response to surgery. While this project is purposely focused on neuropathic pain due to nerve compression at the wrist, identifying the role of brain and spinal cord 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 providing rationale for the development of tailored interventions focused on glial modulation.

在此提案中，我们将通过评估神经炎症在神经性疼痛中的作用 患有常见的诱捕神经病，腕管综合征（CTS）的患者。我们将在临床上 评估并扫描总共100名参与者：80名患有CTS和20名健康志愿者的患者。 所有参与者将在临床上进行评估，并通过集成正电子接收大脑和脊髓成像 发射断层扫描 /磁共振（PET / MR）成像和[11C] PBR28，第二代 18 kDa易位蛋白（TSPO）的放射性物体，我们以前用来证明神经胶质 慢性疼痛患者和神经退行性疾病的激活。将重新扫描并评估患者 在腕管释放手术后第二次临床上。 第一个目的是研究CTS患者中神经炎症的存在。我们假设这一点， 与健康的成年人相比，CTS患者在大脑中会表现出更高的[11C] PBR28 PET信号 （丘脑和主要体感皮质的手表示，S1）和较低的宫颈 脊髓（对应于皮肤C6-C7中正中神经的神经支配区域）。我们 进一步假设较高的大脑/绳索[11C] PBR28 PET信号将与更高的临床疼痛有关， 中位神经传导潜伏期增加，功能不足（即，手指不好和细腻的缺陷） 运动性能）和更严重的神经塑性变化（即S1皮质之间的分离较小 数字2和3的表示形式。 第二个目的是评估手术对神经炎症和神经塑性改变的影响 CTS患者。我们假设手术后三个月，CTS患者平均将证明 与之前的大脑/绳索[11C] PBR28 PET信号和D2/D3 S1分离增加 外科手术。我们还假设这些大脑的变化将彼此相关，并且与 减轻疼痛和功能不足。 最终目的是评估神经炎症和神经塑性变化，以预测对 外科手术。我们假设较高的手术前大脑/绳索[11C] PBR28 PET信号和D2/D3 S1降低 分离将预测对手术的反应较差。 尽管该项目故意专注于由于手腕的神经压缩而引起的神经性疼痛，但 确定大脑和脊髓胶质神经胶质在持续性神经疗法的发展和维持中的作用 人类疼痛和与疼痛有关的残疾将对管理具有重要的实际影响 多种疼痛障碍。例如，它将提供至关重要的人类证据，为 开发针对神经胶质调制的量身定制干预措施。