Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Pain. 2009 Dec 15;147(1-3):265-76. doi: 10.1016/j.pain.2009.09.030. Epub 2009 Oct 22.
Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.
脊髓损伤（SCI）后出现的中枢性神经痛（CNP）按受影响的区域描述：上位、同位和下位疼痛分别发生在 SCI 水平以上、同位和 SCI 水平以下的皮节。患有 SCI 的人和 SCI 的啮齿动物模型会出现上位疼痛，其特征是机械性痛觉过敏和热痛觉过敏。这种疼痛的机制尚不清楚，本研究的目的是阐明导致上位 CNP 产生的因素。在胸椎（T10）挫伤后，前肢伤害感受器自发性活动增强，并且对前爪的机械和热刺激敏感，损伤后 35 天。颈背部角神经元对非伤害性和伤害性机械刺激以及感受野的热刺激表现出增强的反应。免疫染色背根神经节（DRG）细胞和脊髓节段的激活转录因子 3（ATF3，神经元损伤的标志物）排除了神经元损伤是上位敏感化的原因，因为只有少数 C8 DRG 细胞表达 AFT3，并且颈段脊髓只有少数到没有 ATF3 标记的细胞。最后，在 SCI 后 35 天，胸段和颈段脊髓中存在激活的小胶质细胞和星形胶质细胞，表明胶质细胞从损伤部位向头部的激活扩散。基于这些数据，我们得出结论，未受伤的颈髓中的外周和中枢敏化以及反应性胶质细胞导致 CNP。我们假设，颈髓中的反应性胶质细胞释放促炎物质，从而驱动慢性 CNP。因此，上位 CNP 是许多脊髓节段之间复杂的级联事件的结果。
