PMID- 22459482
OWN - NLM
STAT- MEDLINE
DCOM- 20121023
LR  - 20120615
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 88
IP  - 4
DP  - 2012 Jul 1
TI  - High-mobility group box 1 contributes to mechanical allodynia and spinal 
      astrocytic activation in a mouse model of type 2 diabetes.
PG  - 332-7
LID - 10.1016/j.brainresbull.2012.03.002 [doi]
AB  - Chronic pain is one of the most common complications of diabetes. However, 
      current treatments for diabetic pain are usually unrealistic because the 
      underlying mechanisms are far from being clear. Immerging studies have implicated 
      immune factors as key players in the diabetic pain. High-mobility group box 1 
      (HMGB1) is an important mediator of inflammatory response, but its role in 
      diabetic pain is unclear. In the present study, we observed that db/db mice (a 
      model of type 2 diabetes) developed persistent mechanical allodynia from 
      postnatal 2 months. Western blot showed that in postnatal 2-5 months, HMGB1 was 
      significantly higher than that of the heterozygous littermates (db/+) mice. 
      Intrathecal injection of a HMGB1 neutralizing antibody (anti-HMGB1) inhibited 
      mechanical allodynia. Immunostaining data showed that compared with db/+ and C57 
      mice (postnatal 4 months), glial fibrillary acidic protein (GFAP) staining was 
      significantly increased in the spinal cord of db/db mice. Anti-HMGB1 could 
      effectively decrease GFAP expression. Real-time PCR showed that in postnatal 4 
      months, db/db mice induced significant increases of TNF-alpha, IL-1beta, IL-6 and 
      monocyte chemoattractant protein-1 (MCP-1) in the spinal dorsal horn, while 
      anti-HMGB1 (50 mug) effectively inhibited the up-regulation of these inflammatory 
      mediators. Our results indicate that HMGB1 is significantly up-regulated in the 
      spinal cord of type 2 diabetes, and inhibiting HMGB1 may provide a novel 
      treatment for diabetic pain.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Ren, Peng-Cheng
AU  - Ren PC
AD  - Department of Orthopaedics, Tangdu Hospital, the Fourth Military Medical 
      University, Xi'an, Shaanxi Province, China.
FAU - Zhang, Yong
AU  - Zhang Y
FAU - Zhang, Xu-Dong
AU  - Zhang XD
FAU - An, Li-Jun
AU  - An LJ
FAU - Lv, Hai-Gang
AU  - Lv HG
FAU - He, Jun
AU  - He J
FAU - Gao, Chang-Jun
AU  - Gao CJ
FAU - Sun, Xu-De
AU  - Sun XD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120320
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (HMGB1 Protein)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Blotting, Western
MH  - Chronic Pain/etiology/genetics/metabolism
MH  - Diabetes Mellitus, Type 2/complications/genetics/*metabolism
MH  - Disease Models, Animal
MH  - HMGB1 Protein/genetics/*metabolism
MH  - Hyperalgesia/etiology/genetics/*metabolism
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Real-Time Polymerase Chain Reaction
MH  - Spinal Cord/*metabolism
EDAT- 2012/03/31 06:00
MHDA- 2012/10/24 06:00
CRDT- 2012/03/31 06:00
PHST- 2011/11/21 00:00 [received]
PHST- 2012/02/13 00:00 [revised]
PHST- 2012/03/11 00:00 [accepted]
PHST- 2012/03/31 06:00 [entrez]
PHST- 2012/03/31 06:00 [pubmed]
PHST- 2012/10/24 06:00 [medline]
AID - S0361-9230(12)00045-7 [pii]
AID - 10.1016/j.brainresbull.2012.03.002 [doi]
PST - ppublish
SO  - Brain Res Bull. 2012 Jul 1;88(4):332-7. doi: 10.1016/j.brainresbull.2012.03.002. 
      Epub 2012 Mar 20.