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

Yamazaki, Kazuyoshi; Kawabori, Masahito; Seki, Toshitaka; Takamiya, Soichiro; Tateno, Takahiro; Konno, Kotaro; Watanabe, Masahiko; Houkin, Kiyohiro

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

Yamazaki, Kazuyoshi; Kawabori, Masahito; Seki, Toshitaka et al.

Journal of Neurotrauma, 2020, 37, 1720-1728

Permalink : https://hdl.handle.net/2115/79044

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アクセス権	open access
URI	https://hdl.handle.net/2115/79044
タイトル	FTY720 Attenuates Neuropathic Pain after Spinal Cord Injury by Decreasing Systemic and Local Inflammation in a Rat Spinal Cord Compression Model
著者	Yamazaki, Kazuyoshi ; Kawabori, Masahito ; Seki, Toshitaka ; Takamiya, Soichiro ; Tateno, Takahiro ; Konno, Kotaro ; Watanabe, Masahiko ; Houkin, Kiyohiro
著者名 Yamazaki, Kazuyoshi
e-Rad_Researcher 50399870 著者名 Kawabori, Masahito
著者名 Seki, Toshitaka
著者名 Takamiya, Soichiro
著者名 Tateno, Takahiro
e-Rad_Researcher 20599641 著者名 Konno, Kotaro
e-Rad_Researcher 70210945 著者名 Watanabe, Masahiko
e-Rad_Researcher 90229146 著者名 Houkin, Kiyohiro
言語	英語
キーワード	allodynia
	inflammation
	FTY720
	glial scar
	spinal cord injury
発行日	2020-08-01
出版者	Mary Ann Liebert
収録物名	Journal of Neurotrauma
巻(号)	37
ページ	1720-1728
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 4.0 International
権利情報	© 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 (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
PISSN	0897-7151
EISSN	1557-9042
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1089/neu.2019.6905