Transcriptional profiling of spinal cord injury-induced central neuropathic pain
Transcriptional profiling of spinal cord injury-induced central neuropathic pain
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DOI：
10.1111/j.1471-4159.2005.03462.x
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
Perez-Polo, JR
中科院分区：
文献类型：
--
作者：
Nesic, O;Lee, J;Perez-Polo, JR
中枢神经性疼痛（CNP）是脊髓损伤（SCI）后的一个重要问题，严重影响SCI患者的生活质量。与患者人群一样，大多数大鼠在中度SCI后发生显著的异常性疼痛（CNP大鼠）。然而，约10%的SCI大鼠不发展异常性疼痛，或发展比CNP大鼠（非CNP大鼠）显著更少的异常性疼痛。为了确定SCI后CNP发展的转录变化，我们使用了从CNP和非CNP大鼠脊髓中提取的Affyssin DNA微阵列和RNA。DNA微阵列分析显示，在发生CNP的大鼠脊髓中，与炎症和星形胶质细胞活化相关的许多基因的表达显著增加。例如，胶质纤维酸性蛋白（GFAP）和水通道蛋白4（AQP4）的mRNA水平在CNP大鼠中显著增加。我们还发现，GFAP，S100 β和AQP4蛋白升高持续至少9个月，在整个脊髓挫伤，符合慢性本质的CNP。因此，我们假设CNP的发展部分是由于功能失调、长期“过度活化”的星形胶质细胞。虽然，它已被证明，活化的星形胶质细胞与周围神经性疼痛，这还没有被证明以前在CNP后SCI。
Central neuropathic pain (CNP) is an important problem following spinal cord injury (SCI), because it severely affects the quality of life of SCI patients. As in the patient population, the majority of rats develop significant allodynia (CNP rats) after moderate SCI. However, about 10% of SCI rats do not develop allodynia, or develop significantly less allodynia than CNP rats (non-CNP rats). To identify transcriptional changes underlying CNP development after SCI, we used Affymetrix DNA microarrays and RNAs extracted from the spinal cords of CNP and non-CNP rats. DNA microarry analysis showed significantly increased expression of a number of genes associated with inflammation and astrocytic activation in the spinal cords of rats that developed CNP. For example, mRNA levels of glial fibrilary acidic protein (GFAP) and Aquaporin 4 (AQP4) significantly increased in CNP rats. We also found that GFAP, S100 beta and AQP4 protein elevation persisted for at least 9 months throughout contused spinal cords, consistent with the chronic nature of CNP. Thus, we hypothesize that CNP development results, in part, from dysfunctional, chronically "over-activated" astrocytes. Although, it has been shown that activated astrocytes are associated with peripheral neuropathic pain, this has not previously been demonstrated in CNP after SCI.