Lysophosphatidic acid and its receptors LPA1 and LPA3 mediate paclitaxel-induced neuropathic pain in mice.
Lysophosphatidic acid and its receptors LPA1 and LPA3 mediate paclitaxel-induced neuropathic pain in mice.
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DOI：
10.1186/1744-8069-10-71
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发表时间：
2014-11-19
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：
Uchida H;Nagai J;Ueda H
紫杉醇广泛用于治疗实体瘤，但其通过鲜为人知的机制引起神经性疼痛。此前，我们已经证明溶血磷脂酸（LPA）及其受体（LPA1和LPA3）是周围神经损伤引起的神经性疼痛的引发所必需的。本研究旨在阐明 LPA 及其受体是否可以介导紫杉醇引起的神经性疼痛。腹腔内给予紫杉醇引发脊髓背角LPA种类（18:1-、16:0-和18:0-LPA）的产生显着增加。此外，我们发现紫杉醇治疗后脊髓胞质磷脂酶 A2 和钙非依赖性磷脂酶 A2 显着激活。紫杉醇诱导的 LPA 产生不仅通过神经激肽 1 (NK1) 或 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂鞘内预处理完全消除，而且在 LPA1 受体缺陷 (Lpar1−/−) 和 LPA3 受体缺陷 (Lpar3−/−) 小鼠中也被完全消除。此外，NK1或NMDA受体的药理学阻断可防止紫杉醇治疗后针对机械刺激的缩爪阈值降低。重要的是，Lpar1−/− 和 Lpar3−/− 小鼠中不存在紫杉醇诱导的机械异常性疼痛。这些结果表明 LPA1 和 LPA3 受体介导的脊髓 LPA 产生的放大是紫杉醇诱导的神经性疼痛的发生所必需的。
Paclitaxel, which is widely used for the treatment of solid tumors, causes neuropathic pain via poorly understood mechanisms. Previously, we have demonstrated that lysophosphatidic acid (LPA) and its receptors (LPA1 and LPA3) are required for the initiation of peripheral nerve injury-induced neuropathic pain. The present study aimed to clarify whether LPA and its receptors could mediate paclitaxel-induced neuropathic pain. Intraperitoneal administration of paclitaxel triggered a marked increase in production of LPA species (18:1-, 16:0-, and 18:0-LPA) in the spinal dorsal horn. Also, we found significant activations of spinal cytosolic phospholipase A2 and calcium-independent phospholipase A2 after the paclitaxel treatment. The paclitaxel-induced LPA production was completely abolished not only by intrathecal pretreatment with neurokinin 1 (NK1) or N-methyl-D-aspartate (NMDA) receptor antagonist, but also in LPA1 receptor-deficient (Lpar1−/−) and LPA3 receptor-deficient (Lpar3−/−) mice. In addition, the pharmacological blockade of NK1 or NMDA receptor prevented a reduction in the paw withdrawal threshold against mechanical stimulation after paclitaxel treatments. Importantly, the paclitaxel-induced mechanical allodynia was absent in Lpar1−/− and Lpar3−/− mice. These results suggest that LPA1 and LPA3 receptors-mediated amplification of spinal LPA production is required for the development of paclitaxel-induced neuropathic pain.
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影响因子：
3.3
作者：
Nagai J;Uchida H;Matsushita Y;Yano R;Ueda M;Niwa M;Aoki J;Chun J;Ueda H
通讯作者：
Ueda H
DOI：
10.1073/pnas.97.24.13384
发表时间：
2000-11-21
影响因子：
11.1
作者：
Contos, JJA;Fukushima, N;Chun, J
通讯作者：
Chun, J
溴烯醇内酯和三氟甲基酮对巨噬细胞 CA2+-独立磷脂酶 A(2) 的抑制
影响因子：
4.8
作者：
ACKERMANN, EJ;CONDEFRIEBOES, K;DENNIS, EA
通讯作者：
DENNIS, EA
影响因子：
2
作者：
Morishige, Jun-ichi;Urikura, Mai;Satouchi, Kiyoshi
通讯作者：
Satouchi, Kiyoshi
影响因子：
3.6
作者：
Ogawa, K.;Takasu, K.;Kato, A.
通讯作者：
Kato, A.