Possible involvement of the HMGB1/RAGE signaling mechanism in the induction of central post-stroke pain induced by acute global cerebral ischemia

Shinichi Harada, Wataru Matsuura, Keyue Liu, Masahiro Nishibori, Shogo Tokuyama

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Central post-stroke pain (CPSP) is one of the most under-recognized consequences of cerebral stroke, but the development of an effective treatment strategy is urgent. High-mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE, one of the receptors of HMGB1) have recently been shown to be critical in the modulation of nociceptive transduction following peripheral neuropathy. The aim of this study was to determine the interactions between CPSP and HMGB1/RAGE signaling. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. Neuronal damage was estimated by histological analysis on day 3 after BCAO. The expression levels of the HMGB1 protein in the spinal cord and the sciatic nerve were significantly increased on day 3 after BCAO, although no effects of BCAO were noted on RAGE protein expression. BCAO-induced mechanical allodynia was significantly decreased by the intravenous and intrathecal administration of anti-HMGB1 monoclonal antibody. The BCAO-induced increase of phosphorylation of extracellular signal-regulated kinase (ERK) was canceled by the administration of anti-HMGB1 monoclonal antibody. In addition, BCAO-induced mechanical allodynia was significantly decreased by intrathecal administration of U0126, an inhibitor of ERK. The results showed that BCAO-induced mechanical allodynia can be regulated by the activation of HMGB1/RAGE signaling.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalBrain Research
Volume1646
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Brain Ischemia
Carotid Arteries
Stroke
Pain
Hyperalgesia
Extracellular Signal-Regulated MAP Kinases
Monoclonal Antibodies
HMGB1 Protein
Peripheral Nervous System Diseases
Sciatic Nerve
Intravenous Administration
Spinal Cord
Phosphorylation

Keywords

  • Central post-stroke pain
  • Cerebral ischemia
  • High mobility group box-1
  • Receptor for advanced glycation end products

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Possible involvement of the HMGB1/RAGE signaling mechanism in the induction of central post-stroke pain induced by acute global cerebral ischemia. / Harada, Shinichi; Matsuura, Wataru; Liu, Keyue; Nishibori, Masahiro; Tokuyama, Shogo.

In: Brain Research, Vol. 1646, 01.09.2016, p. 433-440.

Research output: Contribution to journalArticle

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