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Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice

BACKGROUND: 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 (LPA(1) and LPA(3)) are required for the initiation of peripheral nerve injury...

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Autores principales: Uchida, Hitoshi, Nagai, Jun, Ueda, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246549/
https://www.ncbi.nlm.nih.gov/pubmed/25411045
http://dx.doi.org/10.1186/1744-8069-10-71
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author Uchida, Hitoshi
Nagai, Jun
Ueda, Hiroshi
author_facet Uchida, Hitoshi
Nagai, Jun
Ueda, Hiroshi
author_sort Uchida, Hitoshi
collection PubMed
description BACKGROUND: 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 (LPA(1) and LPA(3)) 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. RESULTS: 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 A(2) and calcium-independent phospholipase A(2) 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 LPA(1) receptor-deficient (Lpar1(−/−)) and LPA(3) 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. CONCLUSIONS: These results suggest that LPA(1) and LPA(3) receptors-mediated amplification of spinal LPA production is required for the development of paclitaxel-induced neuropathic pain.
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spelling pubmed-42465492014-11-29 Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice Uchida, Hitoshi Nagai, Jun Ueda, Hiroshi Mol Pain Research BACKGROUND: 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 (LPA(1) and LPA(3)) 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. RESULTS: 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 A(2) and calcium-independent phospholipase A(2) 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 LPA(1) receptor-deficient (Lpar1(−/−)) and LPA(3) 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. CONCLUSIONS: These results suggest that LPA(1) and LPA(3) receptors-mediated amplification of spinal LPA production is required for the development of paclitaxel-induced neuropathic pain. BioMed Central 2014-11-19 /pmc/articles/PMC4246549/ /pubmed/25411045 http://dx.doi.org/10.1186/1744-8069-10-71 Text en © Uchida et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Uchida, Hitoshi
Nagai, Jun
Ueda, Hiroshi
Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title_full Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title_fullStr Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title_full_unstemmed Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title_short Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice
title_sort lysophosphatidic acid and its receptors lpa(1) and lpa(3) mediate paclitaxel-induced neuropathic pain in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246549/
https://www.ncbi.nlm.nih.gov/pubmed/25411045
http://dx.doi.org/10.1186/1744-8069-10-71
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