{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:51:13Z","timestamp":1790985073836,"version":"4.1.0"},"reference-count":23,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:p> Recently, we reported that lysophosphatidic acid (LPA) induces long-lasting mechanical allodynia and thermal hyperalgesia as well as demyelination and upregulation of pain-related proteins through one of its cognate receptors, LPA<jats:sub>1<\/jats:sub>. In addition, mice lacking the LPA<jats:sub>1<\/jats:sub> receptor gene ( lpa<jats:sub> 1<\/jats:sub><jats:sup>-\/-<\/jats:sup> mice) lost these nerve injury-induced neuropathic pain behaviors and phenomena. However, since lpa<jats:sub> 1<\/jats:sub><jats:sup>-\/-<\/jats:sup> mice did not exhibit any effects on the basal nociceptive threshold, it is possible that nerve injury-induced neuropathic pain and its machineries are initiated by LPA via defined biosynthetic pathways that involve multiple enzymes. Here, we attempted to clarify the involvement of a single synthetic enzyme of LPA known as autotaxin (ATX) in nerve injury-induced neuropathic pain. Wild-type mice with partial sciatic nerve injury showed robust mechanical allodynia starting from day 3 after the nerve injury and persisting for at least 14 days, along with thermal hyperalgesia. On the other hand, heterozygous mutant mice for the autotaxin gene ( atx<jats:sup>+\/-<\/jats:sup>), which have 50% ATX protein and 50% lysophospholipase D activity compared with wild-type mice, showed approximately 50% recovery of nerve injury-induced neuropathic pain. In addition, hypersensitization of myelinated A[Formula: see text] - or A\u03b4-fiber function following nerve injury was observed in electrical stimuli-induced paw withdrawal tests using a Neurometer\u00ae. The hyperalgesia was completely abolished in lpa<jats:sub> 1<\/jats:sub><jats:sup>-\/-<\/jats:sup> mice, and reduced by 50% in atx<jats:sup>+\/-<\/jats:sup> mice. Taken together, these findings suggest that LPA biosynthesis through ATX is the source of LPA for LPA<jats:sub>1<\/jats:sub> receptor-mediated neuropathic pain. Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as LPA<jats:sub>1<\/jats:sub> receptor and its downstream pathways may represent a novel way to prevent nerve injury-induced neuropathic pain. <\/jats:p>","DOI":"10.1186\/1744-8069-4-6","type":"journal-article","created":{"date-parts":[[2008,2,8]],"date-time":"2008-02-08T19:13:47Z","timestamp":1202498027000},"source":"Crossref","is-referenced-by-count":94,"title":["Autotaxin, a Synthetic Enzyme of Lysophosphatidic Acid (LPA), Mediates the Induction of Nerve-Injured Neuropathic Pain"],"prefix":"10.1177","volume":"4","author":[{"given":"Makoto","family":"Inoue","sequence":"first","affiliation":[{"name":"Division of Molecular Pharmacology and Neuroscience, Nagasaki University, Graduate School of Biomedical Sciences, 1\u201314 Bunkyomachi, Nagasaki 852\u20138521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmacology and Neuroscience, Nagasaki University, Graduate School of Biomedical Sciences, 1\u201314 Bunkyomachi, Nagasaki 852\u20138521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junken","family":"Aoki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerold","family":"Chun","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute, 10550 North Torrey Pines Road, ICND118, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmacology and Neuroscience, Nagasaki University, Graduate School of Biomedical Sciences, 1\u201314 Bunkyomachi, Nagasaki 852\u20138521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2008,1,1]]},"reference":[{"key":"bibr1-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36618-9"},{"key":"bibr2-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1038\/ncb895"},{"key":"bibr3-1744-8069-4-6","first-page":"247","volume":"4","author":"Jalink K","year":"1993","journal-title":"Cell Growth Differ"},{"key":"bibr4-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9930"},{"key":"bibr5-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1038\/nm1060"},{"key":"bibr6-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2004.05.001"},{"key":"bibr7-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2007.02.001"},{"key":"bibr8-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205623200"},{"key":"bibr9-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200204026"},{"key":"bibr10-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605142200"},{"key":"bibr11-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.24.13384"},{"key":"bibr12-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(83)90201-4"},{"key":"bibr13-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00045-1"},{"key":"bibr14-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"bibr15-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046250"},{"key":"bibr16-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.103614"},{"key":"bibr17-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-16"},{"key":"bibr18-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1995.tb01229.x"},{"key":"bibr19-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118728"},{"key":"bibr20-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-08-03221.2003"},{"key":"bibr21-1744-8069-4-6","doi-asserted-by":"crossref","unstructured":"Inoue M, Xie W, Matsushita Y, Chun J, Aoki J, Ueda H: Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid. Neuroscience 2008. Epub ahead of print.","DOI":"10.1016\/j.neuroscience.2007.12.041"},{"key":"bibr22-1744-8069-4-6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02933.x"},{"key":"bibr23-1744-8069-4-6","first-page":"5446","volume":"63","author":"Clair T","year":"2003","journal-title":"Cancer Res"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1186\/1744-8069-4-6","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1186\/1744-8069-4-6","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1186\/1744-8069-4-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T13:50:40Z","timestamp":1741614640000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1186\/1744-8069-4-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,1]]},"references-count":23,"alternative-id":["10.1186\/1744-8069-4-6"],"URL":"https:\/\/doi.org\/10.1186\/1744-8069-4-6","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,1]]},"article-number":"1744-8069-4-6"}}