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

Yuhei Irie, Maho Tsubota, Mariko Maeda, Shiori Hiramoto, Fumiko Sekiguchi, Hiroyasu Ishikura, Hidenori Wake, Masahiro Nishibori, Atsufumi Kawabata

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)112-116
Number of pages5
JournalJournal of Pharmacological Sciences
Volume143
Issue number2
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • Bladder pain syndrome
  • HMGB1
  • Substance P

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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