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: 10656166
• 负责人: Marco Luciano Loggia
• 金额: $ 72.99万
• 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/10656166
• 关键词: Accounting; Adult; Astrocytes; Behavioral; Boston; Brain; Brain imaging; Carpal Tunnel Syndrome; Central Nervous System; Cervical spinal cord structure; Clinical; Coupled; Data; Development; Digit structure; Enzymes; Etiology; Evaluation; Exhibits; Finger Agnosias; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Hand; Human; Image; Intervention; Lesion; Link; Magnetic Resonance Imaging; Maintenance; Measures; Microglia; Motor; Nerve compression syndrome; Neural Conduction; 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; Syndrome; Testing; Thalamic structure; Time; Wrist; afferent nerve; chemokine; chronic pain; chronic pain patient; clinical pain; clinically significant; cytokine; dermatome; glial activation; healthy volunteer; irritation; median nerve; nerve supply; neuroinflammation; neuropathology; 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.

在这项提案中，我们将通过评估神经炎症在神经病理性疼痛中的作用进行研究。 患者患有一种常见的卡压性神经病，腕管综合征(CTS)。我们会在临床上 评估并扫描总共100名参与者：80名CTS患者和20名健康志愿者。 所有参与者都将接受临床评估，并接受集成正电子的脑和脊髓成像 发射断层扫描/磁共振(PET/MR)成像和第二代[11C]PBR28 18 kDa转位蛋白(TSPO)的放射性配体，我们以前曾用它来证明胶质细胞 慢性疼痛患者和神经退行性疾病患者的激活。将对患者进行重新扫描和评估 临床上，第二次是在腕管松解手术后。 第一个目的是调查CTS患者中神经炎症的存在。我们假设， 与健康成人相比，CTS患者脑组织中的[11C]PBR28PET信号更高 (丘脑和初级躯体感觉皮质的手部代表，S1)和下颈部 脊髓(相当于皮肤体C6-C7的正中神经支配区域)。我们 进一步假设较高的脑/脊髓[11C]PBR28 PET信号将与较高的临床疼痛相关， 正中神经传导潜伏期延长，更严重的功能障碍(即更严重的手指失认和罚款 运动能力)和更严重的神经可塑性改变(即，S1皮质之间较小的间隔 数字2和3的表示法)。 第二个目标是评估手术对神经炎症和神经可塑性改变的影响。 CTS患者。我们假设在手术后3个月，CTS患者平均会表现出 与治疗前相比，脑/脊髓[11C]PBR28 PET信号减少，D2/D3 S1分离增加 做手术。我们还假设，这些大脑变化将相互关联，并与 减少疼痛和功能缺陷。 最终目的是评估神经炎症和神经可塑性改变作为治疗反应的预测因子。 做手术。我们假设手术前脑/脊髓[11C]PBR28 PET信号增加，D2/D3 S1降低 分离会预示着对手术的反应会更差。 虽然这个项目专门关注手腕神经压迫引起的神经病理性疼痛， 确定脑和脊髓胶质细胞在持续性神经病发生和维持中的作用 人类的疼痛和疼痛相关的残疾将对管理 广泛的疼痛障碍。例如，它将提供关键的人类证据，为 量身定做的干预措施的发展侧重于神经胶质的调节。