2010年5月
Evidence for De Novo Synthesis of Lysophosphatidic Acid in the Spinal Cord through Phospholipase A(2) and Autotaxin in Nerve Injury-Induced Neuropathic Pain
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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- 巻
- 333
- 号
- 2
- 開始ページ
- 540
- 終了ページ
- 546
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1124/jpet.109.164830
- 出版者・発行元
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
We previously reported that lysophosphatidic acid (LPA) initiates nerve injury-induced neuropathic pain and its underlying mechanisms. In addition, we recently demonstrated that intrathecal injection of LPA induces de novo LPA production through the action of autotaxin (ATX), which converts lysophosphatidylcholine to LPA. Here, we examined nerve injury-induced de novo LPA production by using a highly sensitive biological titration assay with B103 cells expressing LPA(1) receptors. Nerve injury caused high levels of LPA production in the ipsilateral sides of the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve, or sciatic nerve. Nerve injury-induced LPA production reached its maximum at 3 h after injury, followed by a rapid decline by 6 h. The LPA production was significantly attenuated in ATX heterozygous mutant mice, whereas the concentration and activity of ATX in cerebrospinal fluid were not affected by nerve injury. On the other hand, the activities of cytosolic phospholipase A(2) (cPLA(2)) and calcium-independent phospholipase A(2) (iPLA(2)) were enhanced, with peaks at 1 h after injury. Both de novo LPA production and neuropathic pain-like behaviors were substantially abolished by intrathecal injection of arachidonyl trifluoromethyl ketone, a mixed inhibitor of cPLA(2) and iPLA(2), or bromoenol lactone, an iPLA(2) inhibitor, at 1 h after injury. However, administration of these inhibitors at 6 h after injury had no significant effect on neuropathic pain. These findings provide evidence that PLA(2)- and ATX-mediated de novo LPA production in the early phase is involved in nerve injury-induced neuropathic pain.
- リンク情報
- ID情報
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- DOI : 10.1124/jpet.109.164830
- ISSN : 0022-3565
- PubMed ID : 20123931
- Web of Science ID : WOS:000276777900020