PMID- 33811955
OWN - NLM
STAT- MEDLINE
DCOM- 20220207
LR  - 20220207
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 171
DP  - 2021 Jun
TI  - The alpha2delta-1-NMDAR1 interaction in the trigeminal ganglion contributes to orofacial 
      ectopic pain following inferior alveolar nerve injury.
PG  - 162-171
LID - S0361-9230(21)00097-6 [pii]
LID - 10.1016/j.brainresbull.2021.03.019 [doi]
AB  - Orofacial ectopic pain can often arise following nerve injury. However, the exact 
      mechanism responsible for orofacial ectopic pain induced by trigeminal nerve 
      injury remains unknown. The alpha2delta-1 and glutamate N-methyl-d-aspartic acid receptor 
      (NMDAR) interactions have been demonstrated to participate in neuropathic pain 
      regulation in the spinal cord. In this study, a rat model of inferior alveolar 
      nerve transection (IANX) was used to investigate the role of alpha2delta-1-NMDAR1 
      interaction in the trigeminal ganglion (TG) in regard to the regulation of 
      orofacial ectopic pain. Western blot (WB) analysis indicated that alpha2delta-1 and 
      NMDAR1 in the TG were substantially higher in IANX rats than they were in 
      sham/naive rats. Additionally, immunofluorescence (IF) results revealed that 
      alpha2delta-1 and NMDAR1 were co-expressed and distributed within neurons and activated 
      satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated 
      that alpha2delta-1-NMDAR1 complex levels in the TG were higher in IANX rats than they 
      were in sham rats. Furthermore, the results of behavioral tests demonstrated that 
      intra-TG injection of gabapentin (alpha2delta-1 inhibitory ligand) or memantine 
      hydrochloride (NMDAR antagonist) reversed the decrease in mechanical 
      head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of alpha2delta-1 by 
      intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 
      protein, and the inhibition of NMDAR by intra-TG administration of memantine 
      hydrochloride inhibited the increased expression of alpha2delta-1 protein induced by 
      IANX. In conclusion, the physical and functional interaction between alpha2delta-1 and 
      NMDAR1 is critical for the development of orofacial ectopic pain, indicating that 
      alpha2delta-1, NMDAR1, and the alpha2delta-1-NMDAR1 complex may represent potential targets for 
      the treatment of orofacial ectopic pain.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Fu, Min
AU  - Fu M
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Liu, Fei
AU  - Liu F
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Zhang, Yan-Yan
AU  - Zhang YY
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Lin, Jiu
AU  - Lin J
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Huang, Chao-Lan
AU  - Huang CL
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Li, Yue-Ling
AU  - Li YL
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Wang, Hang
AU  - Wang H
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Zhou, Cheng
AU  - Zhou C
AD  - Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience 
      Center, West China Hospital of Sichuan University, Chengdu, China.
FAU - Li, Chun-Jie
AU  - Li CJ
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Shen, Jie-Fei
AU  - Shen JF
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; 
      Department of Prosthodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China. Electronic address: shenjiefei@scu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210331
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Cacna2d1 protein, rat)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Calcium Channels, L-Type/*metabolism
MH  - Facial Pain/etiology/*metabolism
MH  - Male
MH  - Mandibular Nerve/metabolism
MH  - Mandibular Nerve Injuries/*complications
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Trigeminal Ganglion/*metabolism
OTO - NOTNLM
OT  - Inferior alveolar nerve transection
OT  - NMDAR1
OT  - Orofacial ectopic pain
OT  - Trigeminal ganglion
OT  - alpha2delta-1
EDAT- 2021/04/04 06:00
MHDA- 2022/02/08 06:00
CRDT- 2021/04/03 20:09
PHST- 2020/12/21 00:00 [received]
PHST- 2021/03/21 00:00 [revised]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2022/02/08 06:00 [medline]
PHST- 2021/04/03 20:09 [entrez]
AID - S0361-9230(21)00097-6 [pii]
AID - 10.1016/j.brainresbull.2021.03.019 [doi]
PST - ppublish
SO  - Brain Res Bull. 2021 Jun;171:162-171. doi: 10.1016/j.brainresbull.2021.03.019. 
      Epub 2021 Mar 31.