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FTY720 Attenuates Neuropathic Pain after Spinal Cord Injury by Decreasing Systemic and Local Inflammation in a Rat Spinal Cord Compression Model

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Title: FTY720 Attenuates Neuropathic Pain after Spinal Cord Injury by Decreasing Systemic and Local Inflammation in a Rat Spinal Cord Compression Model
Authors: Yamazaki, Kazuyoshi Browse this author
Kawabori, Masahito Browse this author →KAKEN DB
Seki, Toshitaka Browse this author
Takamiya, Soichiro Browse this author
Tateno, Takahiro Browse this author
Konno, Kotaro Browse this author →KAKEN DB
Watanabe, Masahiko Browse this author →KAKEN DB
Houkin, Kiyohiro Browse this author →KAKEN DB
Keywords: allodynia
glial scar
spinal cord injury
Issue Date: 1-Aug-2020
Publisher: Mary Ann Liebert
Journal Title: Journal of Neurotrauma
Volume: 37
Start Page: 1720
End Page: 1728
Publisher DOI: 10.1089/neu.2019.6905
Abstract: Neuropathic pain severely impairs rehabilitation and quality of life after spinal cord injury (SCI). The sphingosine-1-phosphate receptor agonist, FTY720, plays an important protective role in neuronal injury. This study aims to examine the effects of FTY720 in a rat acute SCI model, focusing on neuropathic pain. Female rats with SCI induced by 1-min clip compression were administered vehicle or 1.5mg/kg of FTY720 24 h after the injury. Using the mechanical nociceptive threshold test, we monitored neuropathic pain and performed histological analysis of the pain pathway, including the μ opioid receptor (MOR), hydroxytryptamine transporter (HTT), and calcitonin gene-related peptide (CGRP). Motor score, SCI lesion volume, residual motor axons, inflammatory response, glial scar, and microvascular endothelial dysfunction were also compared between the two groups. FTY720 treatment resulted in significant attenuation of post-traumatic neuropathic pain. It also decreased systemic and local inflammation, thereby reducing the damaged areas and astrogliosis and resulting in motor functional recovery. Whereas there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. Whereas HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuroinflammation, maintenance of the blood?brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain.
Rights: © Kazuyoshi Yamazaki et al., 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 川堀 真人

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