Evidence for de novo synthesis of lysophosphatidic acid in the spinal cord through phospholipase A2 and autotaxin in nerve injury-induced neuropathic pain

The Journal of Pharmacology and Experimental Therapeutics
Lin MaHiroshi Ueda

Abstract

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 LPA1 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 A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2) were enhanced, with peaks at 1 h after injury. Both de novo LPA production and neuropathic pain-like behaviors were substantially abolished by intrathecal i...Continue Reading

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Citations

Aug 21, 2013·Cellular and Molecular Neurobiology·Ryo YanoHiroshi Ueda
Aug 2, 2011·Chemical Reviews·Yulia V ShulgaRichard M Epand
May 25, 2010·Journal of Biochemistry·Keita NakanagaJunken Aoki
Aug 7, 2010·Genome Research·Jonathan NissenbaumAriel Darvasi
Sep 11, 2012·Biochimica Et Biophysica Acta·Hiroshi UedaJun Nagai
Apr 10, 2016·Neuropharmacology·María VelascoGraham K Sheridan
May 7, 2013·Expert Opinion on Therapeutic Patents·Efrosini BarbayianniGeorge Kokotos
Feb 20, 2015·Neuron·Yun C YungJerold Chun
May 16, 2015·Journal of Lipid Research·Lorenzo FedericoGordon B Mills
Mar 20, 2014·Journal of Lipid Research·Yun C YungJerold Chun
Apr 4, 2015·Journal of Lipid Research·Christina C Leslie
Jun 19, 2013·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Sun-Hye ChoiSeung-Yeol Nah
Jul 1, 2020·Investigative Ophthalmology & Visual Science·Sasha M Milbeck, Sanjoy K Bhattacharya
Nov 23, 2017·The Journal of Veterinary Medical Science·Tae TakedaShiro Kurusu
Sep 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Richard R RiveraJerold Chun
Jun 14, 2019·Frontiers in Molecular Neuroscience·Carolina RozaJavier Márquez
Nov 5, 2019·Frontiers in Pharmacology·Tabea Osthues, Marco Sisignano
Nov 6, 2020·Neuromolecular Medicine·Eric Birgbauer
Mar 7, 2021·International Journal of Molecular Sciences·Lisha JoshiWolfgang Sattler
Apr 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sajad FakhriMasoumeh Jorjani
Jul 9, 2021·Biochemical and Biophysical Research Communications·Keigo TanakaHiroshi Ueda

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