Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.
Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.
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DOI：
10.1016/j.pain.2009.09.030
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发表时间：
2009-12-15
期刊：
影响因子：
7.4
通讯作者：
Hulsebosch CE
中科院分区：
文献类型：
--
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
脊髓损伤(SCI)后发生的中枢神经病理性疼痛(CNP)由受影响的区域描述：高于水平、位于水平和低于水平的疼痛分别发生在肩部、在/接近或低于脊髓损伤水平的皮肤体。患有脊髓损伤的人和脊髓损伤的啮齿动物模型患者会出现以上水平的疼痛，其特征是机械性痛觉过敏和热痛觉过敏。这种疼痛的潜在机制尚不清楚，本研究的目的是阐明导致以上水平CNP产生的成分。胸部(T10)挫伤后，前肢伤害性感受器自发活动增强，并在伤后35天对前爪机械刺激和热刺激敏感。颈背角神经元对机械非伤害性刺激和伤害性机械刺激以及感受野的热刺激反应增强。背根神经节(DRG)细胞和脊髓节段用激活转录因子3(ATF3，神经元损伤的标志)进行免疫组织化学染色，排除了神经元损伤是致敏水平以上的原因，因为很少有C8 DRG细胞表达AFT3，颈髓节段几乎没有ATF3标记的细胞。最后，在脊髓损伤后35天，小胶质细胞和星形胶质细胞在胸髓和颈髓中被激活，这表明神经胶质细胞的激活从损伤部位向吻部扩散。根据这些数据，我们得出结论，外周和中枢敏化以及未受损伤的颈髓中的反应性胶质细胞参与了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，横跨许多脊髓节段的复杂的级联事件构成了水平以上的CNP。
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.
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影响因子：
3.3
作者：
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通讯作者：
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