Neuronal plasticity at remote sites causes neuropathic pain after SCI

远端部位的神经元可塑性导致 SCI 后神经性疼痛

• 批准号: 7388160
• 负责人: MEGAN R DETLOFF
• 金额: $ 3.41万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388160
• 关键词: Acute; Affect; Afferent Neurons; Amygdaloid structure; Animals; Axon; Behavior; Biomechanics; Cell Nucleus; Chromosome Pairing; Chronic; Clothing; Communication; Contusions; Data; Development; Environment; Esthesia; Fire - disasters; Functional Magnetic Resonance Imaging; Future; Human; Hyperalgesia; Hypersensitivity; Imaging Techniques; Label; Laboratories; Lead; Lesion; Locomotor Recovery; Lumbar spinal cord structure; Magnetic Resonance Imaging; Modeling; Motor; Natural regeneration; Neuroglia; Neuronal Plasticity; Neurons; Pain; Pathway interactions; Patients; Perception; Peripheral nerve injury; Play; Process; Purpose; Rattus; Recovery; Role; Sensory; Sensory Process; Severities; Site; Skin; Spinal Cord; Spinal cord injury; Stimulus; Suid Herpesvirus 1; Synapses; System; Tactile; Testing; Thalamic structure; Time; Trauma; allodynia; base; cingulate cortex; clinically relevant; dorsal column; dorsal horn; locus ceruleus structure; novel; painful neuropathy; relating to nervous system; research study; response; sensory system

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) often impairs sensory systems causing chronic allodynia and hyperalgesia, two common forms of neuropathic pain. While the recovery of motor systems appears to be exponentialy related to axonal sparing at the epicenter, the recovery of normal sensation appears to be an all or none response. In contusion SCI models, profound hypersensitization occurs with greater than 90% axonal loss at the lesion epicenter and is similar in intensity to the pain produced in classic peripheral nerve injury models. The mechanism of neuropathic pain development has been studied extensively following peripheral nerve injury (PNI), while little is known about the mechanism underlying pain development after central trauma. Recent studies show novel remodeling of descending motor systems after SCI that elicited profound locomotor recovery. Using similar transynaptic labeling and functional magnetic resonance imaging techniques, we will determine the anatomical integrity or novel plasticity of the ascending pain pathways. Preliminary data from our laboratory suggest that profound microglial activation not only occurs within the superficial dorsal horn ten segments caudal to the SCI lesion, but also correlates strongly to the development of chronic hypersensitivity after SCI. Though these data suggest that glia play a significant role in the development of hypersensitivity after SCI, it also suggests that there may be profound effects on the sensory neurons due to glial-neuronal communication and/or an alteration of the local environment where sensory processing occurs. The purpose of this proposal is to ascertain whether sensory changes that occur after spinal cord injury are a result of anatomical and functional changes that occur away from the lesion site in supraspinal regions that are involved in the processing of pain and sensory information such as the ventroposterolateral nucleus of the thalamus Potential changes in these regions may ultimately cause hypersensitivity or the perception of pain. This proposal would show for the first time an anatomical and functional pathway (either the original spared or novel pathway) exists that relays pain and sensory information after SCI. It will provide a basis for targeting future mechanistic studies which will ultimately lead to better, more efficacious treatments for the neuropathic pain which occurs after human SCI.

描述（由申请人提供）：脊髓损伤（SCI）经常损害感觉系统，导致慢性异常性疼痛和痛觉过敏，这是神经性疼痛的两种常见形式。虽然运动系统的恢复似乎与震中的轴突保留呈指数关系，但正常感觉的恢复似乎是全或无反应。在挫伤 SCI 模型中，会出现严重的超敏反应，病变中心的轴突损失超过 90%，其强度与经典周围神经损伤模型中产生的疼痛相似。周围神经损伤（PNI）后神经病理性疼痛发展的机制已被广泛研究，但对中枢创伤后疼痛发展的机制知之甚少。最近的研究表明，脊髓损伤后下行运动系统发生了新的重塑，从而引起了显着的运动恢复。使用类似的突触标记和功能磁共振成像技术，我们将确定上行疼痛通路的解剖完整性或新的可塑性。我们实验室的初步数据表明，小胶质细胞的深度激活不仅发生在 SCI 病变尾部十节浅表背角内，而且与 SCI 后慢性超敏反应的发展密切相关。尽管这些数据表明神经胶质细胞在 SCI 后超敏反应的发展中发挥着重要作用，但它也表明由于神经胶质细胞-神经元通讯和/或发生感觉处理的局部环境的改变可能对感觉神经元产生深远的影响。该提案的目的是确定脊髓损伤后发生的感觉变化是否是由于远离病变部位的脊髓上区域发生的解剖和功能变化造成的，这些区域参与疼痛和感觉信息的处理，例如腹后外侧丘脑核 这些区域的潜在变化最终可能导致过敏或疼痛感。该提案将首次表明存在一条在 SCI 后传递疼痛和感觉信息的解剖和功能通路（原始幸存通路或新通路）。它将为未来的机制研究奠定基础，最终为人类脊髓损伤后发生的神经性疼痛提供更好、更有效的治疗方法。