PMID- 33667472
OWN - NLM
STAT- MEDLINE
DCOM- 20210630
LR  - 20210630
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 186
DP  - 2021 Apr
TI  - Perineural high-mobility group box 1 induces mechanical hypersensitivity through 
      activation of spinal microglia: Involvement of glutamate-NMDA receptor dependent 
      mechanism in spinal dorsal horn.
PG  - 114496
LID - S0006-2952(21)00092-7 [pii]
LID - 10.1016/j.bcp.2021.114496 [doi]
AB  - High mobility box 1 (HMGB1), a damage-associated molecular pattern, has crucial 
      roles in induction of neuropathic pain. Upregulation of HMGB1 around the injured 
      sciatic nerve contributes to mechanical hypersensitivity following partial 
      sciatic nerve ligation (PSNL) of mice. However, central mechanisms mediating 
      perineural HMGB1-induced nociceptive hypersensitivity, especially within the 
      spinal dorsal horn, have not been determined. The current study shows that 
      perineural treatment of naive mice with recombinant HMGB1, which mimics increased 
      HMGB1 around the injured sciatic nerve of PSNL mice, significantly induced 
      activation of microglia, but not astrocytes, in the spinal dorsal horn. 
      Intraperitoneal injection of minocycline, a microglial inhibitor, ameliorated 
      perineural rHMGB1-induced mechanical hypersensitivity. In addition, blockade of 
      spinal N-methyl-D-aspartate (NMDA) receptors significantly prevented perineural 
      rHMGB1-induced mechanical hypersensitivity and microglial activation. In 
      contrast, non-NMDA receptors, neurokinin 1 receptor, colony-stimulating factor 1 
      receptor and P2Y(12) receptor were not involved in perineural rHMGB1-induced 
      mechanical hypersensitivity. Furthermore, repeated perineural treatment with an 
      anti-HMGB1 antibody blocked activation of spinal microglia in PSNL mice. 
      Collectively, the current findings demonstrate that increased HMGB1 around 
      injured sciatic nerve might induce nociceptive hypersensitivity through 
      activation of spinal microglia. Thus, HMGB1-dependent mechanisms between the 
      injured sciatic nerve and spinal dorsal horn could be crucial in induction of 
      neuropathic pain.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Nakamura, Yoki
AU  - Nakamura Y
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan.
FAU - Fukuta, Ayako
AU  - Fukuta A
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan.
FAU - Miyashita, Keita
AU  - Miyashita K
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan.
FAU - Zhang, Fang Fang
AU  - Zhang FF
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan; Institute of Pharmacology, Taishan Medical 
      University.
FAU - Wang, Dengli
AU  - Wang D
AD  - Department of Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Japan.
FAU - Liu, Keyue
AU  - Liu K
AD  - Department of Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Japan.
FAU - Wake, Hidenori
AU  - Wake H
AD  - Department of Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Japan; Department of Pharmacology, 
      Faculty of Medicine, Kindai University, Japan.
FAU - Hisaoka-Nakashima, Kazue
AU  - Hisaoka-Nakashima K
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan.
FAU - Nishibori, Masahiro
AU  - Nishibori M
AD  - Department of Pharmacology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Japan.
FAU - Morioka, Norimitsu
AU  - Morioka N
AD  - Department of Pharmacology, Hiroshima University Graduate School of Biomedical 
      and Health Sciences, Japan. Electronic address: mnori@hiroshima-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210303
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Glutamates)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Excitatory Amino Acid Antagonists/administration & dosage
MH  - Glutamates/*metabolism
MH  - HMGB1 Protein/*metabolism/toxicity
MH  - Humans
MH  - Hyperalgesia/chemically induced/*metabolism
MH  - Injections, Spinal
MH  - Male
MH  - Mice
MH  - Microglia/drug effects/*metabolism
MH  - N-Methylaspartate/administration & dosage
MH  - Peripheral Nerves/drug effects/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Spinal Cord Dorsal Horn/drug effects/*metabolism
OTO - NOTNLM
OT  - Allodynia
OT  - HMGB1
OT  - Microglia
OT  - NMDA receptor
OT  - Neuropathic pain
OT  - Sciatic nerve
EDAT- 2021/03/06 06:00
MHDA- 2021/07/01 06:00
CRDT- 2021/03/05 20:10
PHST- 2021/01/15 00:00 [received]
PHST- 2021/02/24 00:00 [revised]
PHST- 2021/02/25 00:00 [accepted]
PHST- 2021/03/06 06:00 [pubmed]
PHST- 2021/07/01 06:00 [medline]
PHST- 2021/03/05 20:10 [entrez]
AID - S0006-2952(21)00092-7 [pii]
AID - 10.1016/j.bcp.2021.114496 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2021 Apr;186:114496. doi: 10.1016/j.bcp.2021.114496. Epub 2021 
      Mar 3.