Leichsenring Anna, Bäcker Ingo, Wendt Wiebke, Andriske Michael, Schmitz Beate, Stichel Christine C, Lübbert Hermann
Department of Animal Physiology, Ruhr-University of Bochum, Bochum, Germany.
BMC Neurosci. 2008 Aug 12;9:80. doi: 10.1186/1471-2202-9-80.
Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T).
Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different.
The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.
大量证据表明脊髓中的细胞和分子变化对慢性神经性疼痛状态的诱导和持续有着重大贡献。长期以来，蛋白酶主要被视为蛋白质降解酶，但现在它们作为疼痛病理中的信号分子正受到越来越多的关注。在本研究中，我们聚焦于两种组织蛋白酶，组织蛋白酶S（CATS）和组织蛋白酶X（CATX），并研究了它们在大鼠第5腰神经横断模型（L5T）中枢神经系统神经性疼痛发展和进展过程中的时空表达及活性。
损伤后立即观察到，组织蛋白酶CATS和CATX在脊髓中均上调。此外，我们成功测量了CATX的活性，其在L5T后显著增加。这些蛋白质的差异表达在脊髓中呈现相同的空间分布和时间进程，在慢性疼痛后期一直延伸至延髓。然而，CATS和CATX的细胞分布却有很大差异。
CATS和CATX表达改变的细胞分布及时空发展表明，这些蛋白质是参与慢性疼痛诱导和维持的脊髓机制中的重要参与者。
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