Alteration of the lysophosphatidic acid and its precursor lysophosphatidylcholine levels in spinal cord stenosis: A study using a rat cauda equina compression model

Baasanjav Uranbileg,Junken Aoki,Yutaka Yatomi,Masahiko Sumitani,Yoshitsugu Yamada,Ritsumi Saito,Daisuke Saigusa,Miho Sekiguchi,Hitoshi Ikeda,Akira Uruno,Kuniyuki Kano,Nobuko Ito,Makoto Kurano

doi:10.1038/s41598-019-52999-5

Abstract

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.

Highlights

Cauda equina compression (CEC) is a major cause of neurogenic claudication and progresses to neuropathic pain (NP)
The present study showed the possible involvement of lysophospholipids (LPLs), especially the ATX-lysophosphatidic acid (LPA) axis, in neurogenic claudication associated with neuropathic pain of the development of lumbar spinal canal stenosis (LSS)
Using a cauda equina compression (CEC) model, we confirmed that the ATX-LPA axis is enhanced not www.nature.com/scientificreports only in the compressed spinal cord and in the cerebrospinal fluid (CSF) and plasma

Summary

Introduction

Cauda equina compression (CEC) is a major cause of neurogenic claudication and progresses to neuropathic pain (NP). 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 leak out into the CSF. Lumbar spinal canal stenosis (LSS) is the narrowing of the spinal canal and is characterized by the presence of low back pain and radiating leg pain, including cramping muscle pain and tired legs All of these painful symptoms are associated with symptoms of neuropathic pain (NP). In our recent human study, increasing LPA of the cerebrospinal fluids (CSF) was linearly associated with severity of neurogenic claudication and the anatomical narrowing grade of LSS15. Enhancement of the LPC level during NP is still remaining unclear, but for the increased level of the LPA in CSF could be explained from LPC by hydrolyzing action of the ATX that already exits in CSF

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