Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain
Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain
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DOI：
10.1186/1744-8069-5-64
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发表时间：
2009-11-13
期刊：
影响因子：
3.3
通讯作者：
Ueda, Hiroshi
中科院分区：
文献类型：
--
作者：
Ma, Lin;Uchida, Hitoshi;Ueda, Hiroshi
背景：我们之前报道过，鞘内注射溶血磷脂酰胆碱（LPC）可通过激活溶血磷脂酸（LPA）-1受体诱发神经性疼痛，这可能是通过自分泌运动因子（ATX）将LPC转化为LPA来实现的。
结果：我们利用表达LPA(1)受体的B103细胞进行生物滴定测定，对体内LPC诱导的LPA生成情况进行了检测。鞘内给予LPC后，脊髓背角和背根中LPA的生成呈现时间相关性，但在背根神经节、脊神经或坐骨神经中未出现这种情况。在ATX杂合子小鼠中，LPC诱导的LPA生成显著减少，而在LPA(3)受体缺陷的小鼠中，这种生成则完全消失，不过在LPA(1)或LPA(2)受体缺陷的小鼠中并未消失。鞘内给予LPA后，也观察到了类似的具有时间相关性且由LPA(3)受体介导的LPA生成。在一项使用脊髓切片的体外研究中，LPC诱导的LPA生成同样由ATX和LPA(3)受体介导。相比之下，鞘内给予LPA会诱发神经性疼痛，而在LPA(1)或LPA(3)受体缺陷的小鼠中，这种疼痛则不会出现。
结论：这些研究结果表明，前馈性LPA生成与LPA诱导的神经性疼痛有关。
Background: We previously reported that intrathecal injection of lysophosphatidylcholine (LPC) induced neuropathic pain through activation of the lysophosphatidic acid (LPA)-1 receptor, possibly via conversion to LPA by autotaxin (ATX).Results: We examined in vivo LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA(1) receptors. Intrathecal administration of LPC caused time-related production of LPA in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve or sciatic nerve. LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA(3), but not LPA(1) or LPA(2) receptors. Similar time-related and LPA(3) receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an in vitro study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA(3) receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA(1) or LPA(3) receptors.Conclusion: These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.