Nerve injury evoked loss of latexin expression in spinal cord neurons contributes to the development of neuropathic pain.
Nerve injury evoked loss of latexin expression in spinal cord neurons contributes to the development of neuropathic pain.
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神经损伤引起的脊髓神经元中乳胶素表达的丧失有助于神经性疼痛的发展。
DOI：
10.1371/journal.pone.0019270
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Niederberger E
中科院分区：
文献类型：
--
作者：
Kühlein HN;Tegeder I;Möser C;Lim HY;Häussler A;Spieth K;Jennes I;Marschalek R;Beckhaus T;Karas M;Fauth M;Ehnert C;Geisslinger G;Niederberger E
神经损伤导致周围和中枢神经系统的敏化机制，涉及感觉神经的转录和转录后修饰。为了评估备用神经损伤模型 (SNI) 中坐骨神经损伤后脊髓中的蛋白质调节，我们使用二维差异凝胶电泳 (DIGE) 技术进行了蛋白质组分析。在每个凝胶上分离的大约 2300 个蛋白质点中，我们在 SNI 后检测到 55 个显着调节的蛋白质，其中 41 个通过 MALDI-TOF MS 成功鉴定。在 SNI 后 DIGE 分析中受到调节的蛋白质中，我们重点关注羧肽酶 A 抑制剂乳胶蛋白，因为蛋白酶功能障碍会导致神经性疼痛的发生。 SNI 后乳胶蛋白表达降低，这可以通过蛋白质印迹分析、定量 RT-PCR 和原位杂交来证实。乳胶蛋白的减少与羧肽酶 A 活性的增加相关，表明由于脊髓神经元中乳胶蛋白表达的丧失，周围神经损伤后脊髓中乳胶蛋白和羧肽酶 A 之间的平衡受到损害。这可能有助于冷异常性疼痛的发生，因为通过 AAV 介导的乳胶蛋白转导或小分子羧肽酶 A 抑制剂的施用，脊髓中神经元乳胶蛋白表达的正常化显着减少了 SNI 后丙酮诱发的伤害性行为。我们的结果表明蛋白质组学作为筛选工具的有用性，可用于识别神经损伤引起的痛觉过度的新机制，并表明羧肽酶 A 抑制可能有助于减少冷异常性疼痛。
Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.
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影响因子：
4.8
作者：
Corvey, C;Koetter, P;Entian, KD
通讯作者：
Entian, KD
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
5.9
作者：
O'Connor, Alec B.;Dworkin, Robert H.
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Dworkin, Robert H.
影响因子：
5
作者：
Matsugi, Shinji;Hamada, Takatoshi;Satomura, Shinji
通讯作者：
Satomura, Shinji
DOI：
10.1073/pnas.0610811104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Clark, Anna K.;Yip, Ping K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia