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: 7274458
• 负责人: MEGAN R DETLOFF
• 金额: $ 3.35万
• 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/7274458
• 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 Nerves; 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）经常会损害引起慢性异常性异常和痛觉过敏的感觉系统，这是两种常见的神经性疼痛形式。尽管电机系统的恢复似乎与轴突在震中的隔离相关，但正常感觉的恢复似乎是全部或无反应。在挫折SCI模型中，在病变震中时发生了深度超敏反应，轴突损失大于90％，并且强度与经典外周神经损伤模型产生的疼痛相似。在周围神经损伤（PNI）之后，已经对神经性疼痛发育的机制进行了广泛的研究，而对中央创伤后疼痛发育的基本机制知之甚少。最近的研究表明，SCI后对下降运动系统进行了新的重塑，从而引起了深刻的运动恢复。使用类似的透射标记和功能性磁共振成像技术，我们将确定上升疼痛途径的解剖完整性或新颖的可塑性。我们实验室的初步数据表明，深层的小胶质细胞激活不仅发生在浅表背喇叭中十个段与科学病变中，而且与SCI后的慢性超敏性的发展密切相关。尽管这些数据表明胶质在SCI后超敏反应中起着重要作用，但它也表明，由于神经胶质神经元通信和/或发生感官处理的局部环境改变，可能会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从疼痛和感觉信息处理中涉及的病变部位发生的解剖和功能变化的结果，这些区域涉及这些区域的丘脑潜能变化等疼痛和感觉信息，例如这些区域的潜在变化可能会导致痛苦或痛苦或痛苦或痛苦感知。该提案将首次显示出解剖和功能性途径（原始遗憾的途径或新颖的途径），它会在SCI后传达疼痛和感觉信息。它将为靶向未来的机械研究提供一个基础，该研究最终将为人类科学后发生的神经性疼痛带来更好，更有效的治疗方法。