Leukotriene Synthases and the Receptors Induced by Peripheral Nerve Injury in the Spinal Cord Contribute to the Generation of Neuropathic Pain
Leukotriene Synthases and the Receptors Induced by Peripheral Nerve Injury in the Spinal Cord Contribute to the Generation of Neuropathic Pain
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DOI：
10.1002/glia.20948
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发表时间：
2010-04-01
期刊：
影响因子：
6.2
通讯作者：
Noguchi, Koichi
中科院分区：
文献类型：
--
作者：
Okubo, Masamichi;Yamanaka, Hiroki;Noguchi, Koichi
白三烯（Leukotrienes，LT）是一种由花生四烯酸衍生的类花生酸类脂质介质，通过磷脂酶从细胞膜上释放，参与了4种炎症性疾病的发病机制，如哮喘、类风湿性关节炎和外周炎性疼痛。我们使用大鼠备用神经损伤（SNI）模型检测了LTs是否与周围神经损伤后神经病理性疼痛的病理机制有关。我们研究了LT脱氢酶（5-脂氧合酶; 5-LO. 5-LO、FLAP、LTA 4水解酶（LtA 4 h和LTC 4合成酶（LTC 4s））和受体（BLT 1、2和CysLT 1、2）mRNA在大鼠脊髓中的表达。SNI后mRNA增加，但CysLT 2 mRNA没有增加。原位杂交结合免疫组化观察5-LO。皮瓣和CysLT 1 mRNA在脊髓小胶质细胞中表达LTA 4 h和LTC 4s mRNA在脊髓神经元和小胶质细胞中表达131，11 mRNA在脊髓神经元中表达p38丝裂原活化蛋白激酶抑制剂，而不是MEK抑制剂，减少脊髓小胶质细胞中5-LO的增加连续鞘内施用5-LO抑制剂或BLT 1。CysLT1。受体拮抗剂抑制由SNI诱导的机械性异常性疼痛我们的发现表明，通过p38 MAPK产生的脊髓小胶质细胞中LT合成的增加在神经病理性疼痛的产生中起作用。(C)2009威利-利斯公司
Leukotrienes (LTs) belong to a large family of lipid mediators, termed eicosanoids, which are derived from arachidonic acids and released from the cell membrane by phospholipases LTs are involved in the pathogenesis 4 inflammatory diseases, Such as asthma, rheumatoid arthritis, and peripheral inflammatory pain In the present study, we examined whether LTs were implicated in pathomechanism of neuropathic Pain following peripheral nerve injury Using the spared nerve injury (SNI) model in rats. we investigated the expression of LT synthases (5-lipoxygenase; 5-LO. Five lipoxygenase activating protein, FLAP, LTA4 hvdrolase: LtA4h and LTC4 synthase, LTC4s) and receptors (BLT1, 2 and CysLT1, 2) mRNAs in the rat spinal cord Semi-quantitative RT-PCR revealed that 5-LO, FLAP LTC4s, BLT1, and CysLT1. mRNAs increased following SNI, but not CysLT2 mRNAs Using double labeling analysis of in. situ hybridization with immunohistochemistry, we observed that 5-LO. FLAP. and CysLT1 mRNAs were expressed in spinal microglia LTA4h and LTC4s mRNAs were expressed in both spinal neurons and microglia 131,11 mRNA was expressed in spinal neurons The p38 mitogen-activated protein kinase inhibitor, but not MEK inhibitor, reduced the increase in 5-LO in spinal microglia Continuous intrathecal administration of the 5-LO inhibitor or BLT1. and CysLT1. receptor antagonists suppressed mechanical allodynia induced by SNI Our findings suggest that the increase of LT synthesis in spinal microglia produced via p38 MAPK plays a role in the generation of neuropathic pain. (C) 2009 Wiley-Liss, Inc.