Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid
Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid
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DOI：
10.1016/j.neuroscience.2007.12.041
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发表时间：
2008-03-18
期刊：
影响因子：
3.3
通讯作者：
Ueda, H.
中科院分区：
文献类型：
--
作者：
Inoue, M.;Xie, W.;Ueda, H.
溶血磷脂酸受体(LPA(1))信号通路在部分坐骨神经损伤模型中启动神经病理性疼痛和一些病理事件。最近，我们报道了溶血磷脂酸(LPA)通过LPA受体信号通路诱导神经病理性疼痛、脱髓鞘和痛相关蛋白表达的改变。溶血磷脂酰胆碱(LPC)，也被称为溶血磷脂，由自体趋化蛋白/ATX水解成LPA，引起类似的可塑性变化。在此，我们试图阐明ATX和LPA(1)受体信号是否参与LPC诱导的神经病理性疼痛。在野生型小鼠中，单个鞘内(I.T.)注射LPC后2天出现机械性痛觉过敏和热痛敏，至少持续7天。另一方面，在缺乏LPA受体基因的小鼠中，LPC诱导的机械痛敏和热痛敏完全消除。此外，LPC诱导的反应也是显著的，但在ATX基因杂合突变小鼠中部分降低。这些发现表明，鞘内注射的LPC被ATX转化为LPA，这种LPA激活LPA受体，启动神经病理性疼痛。(C)2008年IBRO。爱思唯尔有限公司出版。保留所有权利。
Lysophosphatidic acid receptor (LPA(1)) signaling initiates neuropathic pain and several pathological events in a partial sciatic nerve injury model. Recently, we reported that lysophosphatidic acid (LPA) induces neuropathic pain as well as demyelination and pain-related protein expression changes via LPA, receptor signaling. Lysophosphatidylcholine (LPC), also known as lysolecithin, which is hydrolyzed by autotaxin/ATX into LPA, induces similar plastic changes. Here, we attempted to clarify whether ATX and LPA(1) receptor signaling is involved in the LPC-induced neuropathic pain. In wild-type mice, a single intrathecal (i.t.) injection of LPC induced mechanical allodynia and thermal hyperalgesia 2 days after injection; this persisted for 7 days at least. On the other hand, LPC-induced mechanical allodynia and thermal hyperalgesia were completely abolished in mice lacking an LPA, receptor gene. Furthermore, the LPC-induced response was also significantly, but partially reduced in heterozygous mutant mice for the ATX gene. These findings suggest that intrathecally-injected LPC is converted to LPA by ATX, and this LPA activates the LPA, receptor to initiate neuropathic pain. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.