HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model

HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model

HMGB1, a nuclear protein, once released to the extracellular space, promotes somatic and visceral pain signals. We thus analyzed the role of HMGB1 in an intravesical substance P-induced bladder pain syndrome (BPS) mouse model. Intravesical administration of substance P caused referred hyperalgesia/a...

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Main Authors: Yuhei Irie, Maho Tsubota, Mariko Maeda, Shiori Hiramoto, Fumiko Sekiguchi, Hiroyasu Ishikura, Hidenori Wake, Masahiro Nishibori, Atsufumi Kawabata
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Journal of Pharmacological Sciences
Subjects:
HMGB1
Substance P
Bladder pain syndrome
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861320300293
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spelling doaj-62b036e0978d4184865ea5c0f6eb2f7d2020-11-25T02:51:33ZengElsevierJournal of Pharmacological Sciences1347-86132020-06-011432112116HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse modelYuhei Irie0Maho Tsubota1Mariko Maeda2Shiori Hiramoto3Fumiko Sekiguchi4Hiroyasu Ishikura5Hidenori Wake6Masahiro Nishibori7Atsufumi Kawabata8Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, Japan; Division of Emergency and Critical Care Medicine, Fukuoka University, Hospital, Fukuoka, 814-0180, JapanLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, JapanLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, JapanLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, JapanLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, JapanDivision of Emergency and Critical Care Medicine, Fukuoka University, Hospital, Fukuoka, 814-0180, JapanDepartment of Pharmacology, Okayama University Graduate School of Medicine, Okayama, 700-8558, JapanDepartment of Pharmacology, Okayama University Graduate School of Medicine, Okayama, 700-8558, JapanLaboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 577-8502, Japan; Corresponding author. Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan. Fax: +81 6 6730 1394.HMGB1, a nuclear protein, once released to the extracellular space, promotes somatic and visceral pain signals. We thus analyzed the role of HMGB1 in an intravesical substance P-induced bladder pain syndrome (BPS) mouse model. Intravesical administration of substance P caused referred hyperalgesia/allodynia in the lower abdomen and hindpaw without producing severe urothelial damage, which was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin α capable of inactivating HMGB1 and antagonists of RAGE or CXCR4. The HMGB1 inactivation or RAGE blockade also reversed the established bladder pain symptoms. HMGB1 and RAGE are thus considered to serve as therapeutic targets for BPS.http://www.sciencedirect.com/science/article/pii/S1347861320300293HMGB1Substance PBladder pain syndrome
collection DOAJ
language English
format Article
sources DOAJ
author Yuhei Irie
Maho Tsubota
Mariko Maeda
Shiori Hiramoto
Fumiko Sekiguchi
Hiroyasu Ishikura
Hidenori Wake
Masahiro Nishibori
Atsufumi Kawabata
spellingShingle Yuhei Irie
Maho Tsubota
Mariko Maeda
Shiori Hiramoto
Fumiko Sekiguchi
Hiroyasu Ishikura
Hidenori Wake
Masahiro Nishibori
Atsufumi Kawabata
HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
Journal of Pharmacological Sciences
HMGB1
Substance P
Bladder pain syndrome
author_facet Yuhei Irie
Maho Tsubota
Mariko Maeda
Shiori Hiramoto
Fumiko Sekiguchi
Hiroyasu Ishikura
Hidenori Wake
Masahiro Nishibori
Atsufumi Kawabata
author_sort Yuhei Irie
title HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
title_short HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
title_full HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
title_fullStr HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
title_full_unstemmed HMGB1 and its membrane receptors as therapeutic targets in an intravesical substance P-induced bladder pain syndrome mouse model
title_sort hmgb1 and its membrane receptors as therapeutic targets in an intravesical substance p-induced bladder pain syndrome mouse model
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2020-06-01
description HMGB1, a nuclear protein, once released to the extracellular space, promotes somatic and visceral pain signals. We thus analyzed the role of HMGB1 in an intravesical substance P-induced bladder pain syndrome (BPS) mouse model. Intravesical administration of substance P caused referred hyperalgesia/allodynia in the lower abdomen and hindpaw without producing severe urothelial damage, which was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin α capable of inactivating HMGB1 and antagonists of RAGE or CXCR4. The HMGB1 inactivation or RAGE blockade also reversed the established bladder pain symptoms. HMGB1 and RAGE are thus considered to serve as therapeutic targets for BPS.
topic HMGB1
Substance P
Bladder pain syndrome
url http://www.sciencedirect.com/science/article/pii/S1347861320300293
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