PMID- 36187288
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221004
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 16
DP  - 2022
TI  - N-Methyl D-aspartate receptor subtype 2B/Ca(2+)/calmodulin-dependent protein 
      kinase II signaling in the lateral habenula regulates orofacial allodynia and 
      anxiety-like behaviors in a mouse model of trigeminal neuralgia.
PG  - 981190
LID - 10.3389/fncel.2022.981190 [doi]
LID - 981190
AB  - Trigeminal neuralgia (TN) is a peripheral nerve disorder often accompanied by 
      abnormalities in mood. The lateral habenula (LHb) plays important roles in the 
      modulation of pain and emotion. In the present study, we investigated the 
      involvement of the LHb in the mechanisms underlying allodynia and anxiety induced 
      by partial transection of the infraorbital nerve (pT-ION) in mice. Our results 
      indicated that pT-ION induced persistent orofacial allodynia and anxiety-like 
      behaviors, which were correlated with increased phosphorylation of N-Methyl 
      D-aspartate receptor (NMDAR) subtype 2B (p-NR2B) and Ca(2+)/calmodulin-dependent 
      protein kinase II (p-CaMKII) in LHb neurons. Bilateral inhibition of NMDARs and 
      CaMKII in the LHb attenuated the allodynia and anxiety-like behavior induced by 
      pT-ION. Furthermore, bilateral activation of NMDARs in the LHb increased the 
      expression of p-NR2B and p-CaMKII and induced orofacial allodynia and 
      anxiety-like behaviors in naive mice. Adeno-associated virus (AAV)-mediated 
      expression of hM3D(Gq) in CaMKII(+) neurons of the bilateral LHb, followed by 
      clozapine-N-oxide (CNO) administration, also triggered orofacial allodynia and 
      anxiety-like behaviors in naive mice with successful virus infection in LHb 
      neurons (verified based on immunofluorescence). In conclusion, these findings 
      suggest that activation of NMDA/CaMKII signaling in the LHb contributes to the 
      occurrence and development of TN and related anxiety-like behaviors. Therefore, 
      suppressing the activity of CaMKII(+) neurons in the bilateral LHb by targeting 
      NMDA/CaMKII may represent a novel strategy for treating pain and anxiety 
      associated with TN.
CI  - Copyright (c) 2022 Zhuang, Wu, Song, Li, Cui, Yang, Xu and Cui.
FAU - Zhuang, Zi-Fan
AU  - Zhuang ZF
AD  - College of First Clinical Medicine, Beijing University of Chinese Medicine, 
      Beijing, China.
FAU - Wu, Hong-Yun
AU  - Wu HY
AD  - Department of Neurology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Song, Ya-Yi
AU  - Song YY
AD  - Department of Traditional Chinese Medicine, Lianyungang Maternal and Child Health 
      Hospital, Lianyungang, China.
FAU - Li, Lei
AU  - Li L
AD  - Department of Cardiology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Cui, Xia
AU  - Cui X
AD  - Department of Neurology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Yang, Jie
AU  - Yang J
AD  - Department of Neurology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Xu, Xiang-Qing
AU  - Xu XQ
AD  - Department of Neurology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
FAU - Cui, Wen-Qiang
AU  - Cui WQ
AD  - Department of Neurology, Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20220914
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC9521491
OTO - NOTNLM
OT  - Ca2+/calmodulin-dependent protein kinase II (CaMKII)
OT  - N-methyl-D-aspartate receptor (NMDAr)
OT  - anxiety
OT  - lateral habenula
OT  - trigeminal neuralgia
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/04 06:01
PMCR- 2022/01/01
CRDT- 2022/10/03 04:48
PHST- 2022/06/29 00:00 [received]
PHST- 2022/08/22 00:00 [accepted]
PHST- 2022/10/03 04:48 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/04 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2022.981190 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2022 Sep 14;16:981190. doi: 10.3389/fncel.2022.981190. 
      eCollection 2022.