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

基本信息

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
项目类别：
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

项目摘要

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.

在本提案中，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卡压性神经病——腕管综合征（CTS）的患者。我们将在临床上对总共 100 名参与者进行评估和扫描：80 名患有 CTS 的患者和 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大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 易位蛋白 (TSPO) 的放射性配体，我们之前曾用它来证明神经胶质细胞慢性疼痛患者和神经退行性疾病患者的激活。患者将被重新扫描和评估临床上第二次是在腕管松解手术后进行。第一个目标是调查 CTS 患者是否存在神经炎症。我们假设，与健康成年人相比，CTS 患者的大脑中会表现出更高的 [11C]PBR28 PET 信号（丘脑和初级体感皮层的手代表，S1）和下颈椎脊髓（对应于皮节 C6-C7 中正中神经的神经支配区域）。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增加，功能缺陷更严重（即，手指失认能力更差，手指失认能力更差）运动表现）和更严重的神经塑性变化（即 S1 皮质之间的间距更小）数字 2 和 3 的表示）。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 3 个月，CTS 患者平均会表现出与之前相比，脑/脊髓 [11C]PBR28 PET 信号减少，D2/D3 S1 分离增加外科手术。我们还假设这些大脑变化将相互关联，并且与减少疼痛和功能缺陷。最终目标是评估神经炎症和神经塑性改变作为反应的预测因素外科手术。我们假设术前大脑/脊髓 [11C]PBR28 PET 信号较高且 D2/D3 S1 减少分离将预示手术反应较差。虽然这个项目的重点是手腕神经受压引起的神经性疼痛，确定大脑和脊髓神经胶质细胞在持续性神经病变的发展和维持中的作用人类疼痛和与疼痛相关的残疾将对疾病的管理产生重要的实际影响。广泛的疼痛疾病。例如，它将提供重要的人类证据，为开发针对神经胶质细胞调节的定制干预措施。