Abstract
Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain. However, the cellular basis for chronic pain-mediated major depression remains unclear. High-mobility group box 1 protein (HMGB1) has a key role in innate immune responses and appears to be have a role in mediating diverse disorders, including neuropathic pain and depression. The current study aimed to characterize neuropathic pain-induced changes in affect over time and to determine whether HMGB1 has a role in neuropathic pain-induced changes in affect. Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Anxiodepressive-like behaviors in mice were evaluated over 10 weeks, in the social interaction, forced swim, and novelty suppressed feeding tests. Mice developed anxiodepressive-like behavior 6 to 8 weeks after induction of neuropathy. Accompanying anxiodepressive-like behavior, increased HMGB1 protein and microglia activation were observed in frontal cortex at 8 weeks after PSNL. Intracerebroventricular administration of rHMGB1 in naïve mice induced anxiodepressive-like behavior and microglia activation. Blockage of HMGB1 in PSNL mice with glycyrrhizic acid (GZA) or anti-HMGB1 antibody reduced microglia activation and anxiodepressive-like behavior. These results indicate that PSNL-induced anxiodepressive-like behavior is likely mediated by HMGB1. Furthermore, the data indicate that inhibition of HMGB1-dependent microglia activation could be a strategy for the treatment of depression associated with neuropathic pain.
| Original language | English |
|---|---|
| Pages (from-to) | 347-362 |
| Number of pages | 16 |
| Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume | 92 |
| DOIs | |
| Publication status | Published - Jun 8 2019 |
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Keywords
- Depression
- HMGB1
- Microglia
- Neuropathic pain
ASJC Scopus subject areas
- Pharmacology
- Biological Psychiatry
Cite this
High-mobility group box 1-mediated microglial activation induces anxiodepressive-like behaviors in mice with neuropathic pain. / Hisaoka-Nakashima, Kazue; Tomimura, Yoshiaki; Yoshii, Toshiki; Ohata, Kazuto; Takada, Naoki; Zhang, Fang Fang; Nakamura, Yoki; Liu, Keyue; Wake, Hidenori; Nishibori, Masahiro; Nakata, Yoshihiro; Morioka, Norimitsu.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 92, 08.06.2019, p. 347-362.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High-mobility group box 1-mediated microglial activation induces anxiodepressive-like behaviors in mice with neuropathic pain
AU - Hisaoka-Nakashima, Kazue
AU - Tomimura, Yoshiaki
AU - Yoshii, Toshiki
AU - Ohata, Kazuto
AU - Takada, Naoki
AU - Zhang, Fang Fang
AU - Nakamura, Yoki
AU - Liu, Keyue
AU - Wake, Hidenori
AU - Nishibori, Masahiro
AU - Nakata, Yoshihiro
AU - Morioka, Norimitsu
PY - 2019/6/8
Y1 - 2019/6/8
N2 - Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain. However, the cellular basis for chronic pain-mediated major depression remains unclear. High-mobility group box 1 protein (HMGB1) has a key role in innate immune responses and appears to be have a role in mediating diverse disorders, including neuropathic pain and depression. The current study aimed to characterize neuropathic pain-induced changes in affect over time and to determine whether HMGB1 has a role in neuropathic pain-induced changes in affect. Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Anxiodepressive-like behaviors in mice were evaluated over 10 weeks, in the social interaction, forced swim, and novelty suppressed feeding tests. Mice developed anxiodepressive-like behavior 6 to 8 weeks after induction of neuropathy. Accompanying anxiodepressive-like behavior, increased HMGB1 protein and microglia activation were observed in frontal cortex at 8 weeks after PSNL. Intracerebroventricular administration of rHMGB1 in naïve mice induced anxiodepressive-like behavior and microglia activation. Blockage of HMGB1 in PSNL mice with glycyrrhizic acid (GZA) or anti-HMGB1 antibody reduced microglia activation and anxiodepressive-like behavior. These results indicate that PSNL-induced anxiodepressive-like behavior is likely mediated by HMGB1. Furthermore, the data indicate that inhibition of HMGB1-dependent microglia activation could be a strategy for the treatment of depression associated with neuropathic pain.
AB - Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain. However, the cellular basis for chronic pain-mediated major depression remains unclear. High-mobility group box 1 protein (HMGB1) has a key role in innate immune responses and appears to be have a role in mediating diverse disorders, including neuropathic pain and depression. The current study aimed to characterize neuropathic pain-induced changes in affect over time and to determine whether HMGB1 has a role in neuropathic pain-induced changes in affect. Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Anxiodepressive-like behaviors in mice were evaluated over 10 weeks, in the social interaction, forced swim, and novelty suppressed feeding tests. Mice developed anxiodepressive-like behavior 6 to 8 weeks after induction of neuropathy. Accompanying anxiodepressive-like behavior, increased HMGB1 protein and microglia activation were observed in frontal cortex at 8 weeks after PSNL. Intracerebroventricular administration of rHMGB1 in naïve mice induced anxiodepressive-like behavior and microglia activation. Blockage of HMGB1 in PSNL mice with glycyrrhizic acid (GZA) or anti-HMGB1 antibody reduced microglia activation and anxiodepressive-like behavior. These results indicate that PSNL-induced anxiodepressive-like behavior is likely mediated by HMGB1. Furthermore, the data indicate that inhibition of HMGB1-dependent microglia activation could be a strategy for the treatment of depression associated with neuropathic pain.
KW - Depression
KW - HMGB1
KW - Microglia
KW - Neuropathic pain
UR - http://www.scopus.com/inward/record.url?scp=85061820083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061820083&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2019.02.005
DO - 10.1016/j.pnpbp.2019.02.005
M3 - Article
C2 - 30763674
AN - SCOPUS:85061820083
VL - 92
SP - 347
EP - 362
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
ER -