Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis

Abstract Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotax...

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Autores principales:	Baasanjav Uranbileg, Nobuko Ito, Makoto Kurano, Kuniyuki Kano, Kanji Uchida, Masahiko Sumitani, Junken Aoki, Yutaka Yatomi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b88f183c5dc48c3a8dfbb407525812e
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spelling	oai:doaj.org-article:6b88f183c5dc48c3a8dfbb407525812e2021-12-02T10:54:30ZInhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis10.1038/s41598-021-83569-32045-2322https://doaj.org/article/6b88f183c5dc48c3a8dfbb407525812e2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83569-3https://doaj.org/toc/2045-2322Abstract Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA1 receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possible potential efficacy of the ATX inhibitor for NP treatment, we used an NP model with compression of DRG (CD model) and investigated LPA dynamics and whether ATX inhibition could ameliorate NP symptoms, using an orally available ATX inhibitor (ONO-8430506) at a dose of 30 mg/kg. In CD model, we observed increased LPC and LPA levels in CSF, and decreased threshold of the pain which were ameliorated by oral administration of the ATX inhibitor with decreased microglia and astrocyte populations at the site of the spinal dorsal horn projecting from injured DRG. These results suggested possible efficacy of ATX inhibitor for the treatment of NP caused by spinal nerve root compression and involvement of the ATX-LPA axis in the mechanism of NP induction.Baasanjav UranbilegNobuko ItoMakoto KuranoKuniyuki KanoKanji UchidaMasahiko SumitaniJunken AokiYutaka YatomiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Baasanjav Uranbileg Nobuko Ito Makoto Kurano Kuniyuki Kano Kanji Uchida Masahiko Sumitani Junken Aoki Yutaka Yatomi Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
description	Abstract Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA1 receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possible potential efficacy of the ATX inhibitor for NP treatment, we used an NP model with compression of DRG (CD model) and investigated LPA dynamics and whether ATX inhibition could ameliorate NP symptoms, using an orally available ATX inhibitor (ONO-8430506) at a dose of 30 mg/kg. In CD model, we observed increased LPC and LPA levels in CSF, and decreased threshold of the pain which were ameliorated by oral administration of the ATX inhibitor with decreased microglia and astrocyte populations at the site of the spinal dorsal horn projecting from injured DRG. These results suggested possible efficacy of ATX inhibitor for the treatment of NP caused by spinal nerve root compression and involvement of the ATX-LPA axis in the mechanism of NP induction.
format	article
author	Baasanjav Uranbileg Nobuko Ito Makoto Kurano Kuniyuki Kano Kanji Uchida Masahiko Sumitani Junken Aoki Yutaka Yatomi
author_facet	Baasanjav Uranbileg Nobuko Ito Makoto Kurano Kuniyuki Kano Kanji Uchida Masahiko Sumitani Junken Aoki Yutaka Yatomi
author_sort	Baasanjav Uranbileg
title	Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
title_short	Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
title_full	Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
title_fullStr	Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
title_full_unstemmed	Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
title_sort	inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6b88f183c5dc48c3a8dfbb407525812e
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Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis

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