Krämer Heidrun H, He Lan, Lu Bao, Birklein Frank, Sommer Claudia
Department of Neurology, Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55101, Germany.
Neurobiol Dis. 2009 Aug;35(2):177-83. doi: 10.1016/j.nbd.2008.11.002. Epub 2008 Nov 20.
The complex regional pain syndrome (CRPS) is characterized by enhanced neurogenic inflammation, mediated by neuropeptides. Neutral endopeptidase (NEP) is a key enzyme in neuropeptide catabolism. We used NEP knock out (ko) mice to investigate whether NEP deficiency leads to increased pain behavior and signs of neurogenic inflammation after soft tissue trauma with and without nerve injury. After chronic constriction injury (CCI) of the right sciatic nerve, NEP ko mice were more sensitive to heat, to mechanical stimuli, and to cold than wild type mice. Tissue injury without nerve injury produced no differences between genotypes. After CCI, NEP ko mice showed increased hind paw edema but lower skin temperatures than wild type mice. Substance P (SP) and endothelin 1 (ET 1) determined by enzyme immuno assay (EIA) were increased in sciatic nerves from NEP ko mice after CCI. Tissue CGRP content did not differ between the genotypes. The results provide evidence that pain behavior and neurogenic inflammation are enhanced in NEP ko mice after nerve injury. These findings resemble human 'cold' CRPS and suggest that ET 1 plays an important role in the pathogenesis of CRPS with nerve injury.
复杂性区域疼痛综合征（CRPS）的特征是由神经肽介导的神经源性炎症增强。中性内肽酶（NEP）是神经肽分解代谢中的关键酶。我们使用NEP基因敲除（ko）小鼠来研究NEP缺乏是否会导致在有或没有神经损伤的软组织创伤后疼痛行为增加和神经源性炎症迹象。在右侧坐骨神经慢性缩窄损伤（CCI）后，NEP基因敲除小鼠比野生型小鼠对热、机械刺激和冷更敏感。没有神经损伤的组织损伤在不同基因型之间未产生差异。CCI后，NEP基因敲除小鼠后爪水肿增加，但皮肤温度低于野生型小鼠。通过酶免疫测定（EIA）测定的P物质（SP）和内皮素1（ET 1）在CCI后NEP基因敲除小鼠的坐骨神经中增加。不同基因型之间组织降钙素基因相关肽（CGRP）含量没有差异。结果提供了证据表明神经损伤后NEP基因敲除小鼠的疼痛行为和神经源性炎症增强。这些发现类似于人类的“冷”CRPS，并表明ET 1在伴有神经损伤的CRPS发病机制中起重要作用。
