TY - JOUR
T1 - Alteration of the lysophosphatidic acid and its precursor lysophosphatidylcholine levels in spinal cord stenosis
T2 - A study using a rat cauda equina compression model
AU - Uranbileg, Baasanjav
AU - Ito, Nobuko
AU - Kurano, Makoto
AU - Saigusa, Daisuke
AU - Saito, Ritsumi
AU - Uruno, Akira
AU - Kano, Kuniyuki
AU - Ikeda, Hitoshi
AU - Yamada, Yoshitsugu
AU - Sumitani, Masahiko
AU - Sekiguchi, Miho
AU - Aoki, Junken
AU - Yatomi, Yutaka
N1 - Funding Information:
The authors thank Hasegawa K. and Totsu T. from the Department of Anesthesiology and the Pain Relief Center, The University of Tokyo, Tokyo, Japan for their valuable support and technical assistance. This work was supported by Leading Advanced Projects for Medical Innovation (LEAP) from AMED, a Grant-in-Aid for Scientific Research on Innovative Areas 15H05906 (Y.Y.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Cauda equina compression (CEC) is a major cause of neurogenic claudication and progresses to neuropathic pain (NP). A lipid mediator, lysophosphatidic acid (LPA), is known to induce NP via the LPA1 receptor. To know a possible mechanism of LPA production in neurogenic claudication, we determined the levels of LPA, lysophosphatidylcholine (LPC) and LPA-producing enzyme autotaxin (ATX), in the cerebrospinal fluid (CSF) and spinal cord (SC) using a CEC as a possible model of neurogenic claudication. Using silicon blocks within the lumbar epidural space, we developed a CEC model in rats with motor dysfunction. LPC and LPA levels in the CSF were significantly increased from day 1. Importantly, specific LPA species (16:0, 18:2, 20:4) were upregulated, which have been shown to produce by ATX detected in the CSF, without changes on its level. In SC, the LPC and LPA levels did not change, but mass spectrometry imaging analysis revealed that LPC was present in a region where the silicon blocks were inserted. These results propose a model for LPA production in SC and CSF upon neurogenic claudication that LPC produced locally by tissue damages is converted to LPA by ATX, which then leak out into the CSF.
AB - Cauda equina compression (CEC) is a major cause of neurogenic claudication and progresses to neuropathic pain (NP). A lipid mediator, lysophosphatidic acid (LPA), is known to induce NP via the LPA1 receptor. To know a possible mechanism of LPA production in neurogenic claudication, we determined the levels of LPA, lysophosphatidylcholine (LPC) and LPA-producing enzyme autotaxin (ATX), in the cerebrospinal fluid (CSF) and spinal cord (SC) using a CEC as a possible model of neurogenic claudication. Using silicon blocks within the lumbar epidural space, we developed a CEC model in rats with motor dysfunction. LPC and LPA levels in the CSF were significantly increased from day 1. Importantly, specific LPA species (16:0, 18:2, 20:4) were upregulated, which have been shown to produce by ATX detected in the CSF, without changes on its level. In SC, the LPC and LPA levels did not change, but mass spectrometry imaging analysis revealed that LPC was present in a region where the silicon blocks were inserted. These results propose a model for LPA production in SC and CSF upon neurogenic claudication that LPC produced locally by tissue damages is converted to LPA by ATX, which then leak out into the CSF.
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U2 - 10.1038/s41598-019-52999-5
DO - 10.1038/s41598-019-52999-5
M3 - Article
C2 - 31719574
AN - SCOPUS:85074906511
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 16578
ER -