PMID- 34899191
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211215
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 15
DP  - 2021
TI  - The Up-regulation of TNF-alpha Maintains Trigeminal Neuralgia by Modulating MAPKs 
      Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.
PG  - 764141
LID - 10.3389/fncel.2021.764141 [doi]
LID - 764141
AB  - Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous 
      available medical interventions, the therapeutic effects are not ideal. To 
      control the pain attacks, the need for more contemporary drugs continues to be a 
      real challenge. Our previous study reported that Ca(2+)-activated K(+) channels 
      (BK (Ca) ) channels modulated by mitogen-activated protein kinases (MAPKs) in the 
      trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some 
      research studies demonstrated that inflammatory cytokine tumor necrosis factor 
      alpha (TNF-alpha) could promote neuropathic pain. Meanwhile, the trigeminal nucleus 
      caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is 
      responsible for processing sensory and pain signals from the peripheral orofacial 
      area. Thus, this study is aimed to further investigate whether TNF-alpha and MAPKs 
      phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BK 
      (Ca) channels. The results showed that TNF-alpha of the TNC region is upregulated 
      significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) 
      rats model, which displayed persistent facial mechanical allodynia. The normal 
      rats with target injection of exogenous TNF-alpha to the fourth brain ventricle 
      behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold 
      decreased clearly. Meanwhile, the exogenous TNF-alpha increased the action potential 
      frequency and reduced the BK (Ca) currents of TNC neurons significantly, which 
      could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, 
      U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial 
      mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI 
      model rats, respectively. Taken together, our work suggests that the upregulation 
      of TNF-alpha in the TNC region would cause the increase of MAPKs phosphorylation and 
      then the negative regulation of BK (Ca) channels, resulting in the TN.
CI  - Copyright (c) 2021 Lu, Fan, Yu, Ma and Cheng.
FAU - Lu, Zhan-Ying
AU  - Lu ZY
AD  - Experimental Training Center of Basic Medical Science, Naval Medical University, 
      Shanghai, China.
FAU - Fan, Juan
AU  - Fan J
AD  - Experimental Training Center of Basic Medical Science, Naval Medical University, 
      Shanghai, China.
FAU - Yu, Li-Hua
AU  - Yu LH
AD  - Experimental Training Center of Basic Medical Science, Naval Medical University, 
      Shanghai, China.
FAU - Ma, Bei
AU  - Ma B
AD  - Experimental Training Center of Basic Medical Science, Naval Medical University, 
      Shanghai, China.
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the 
      Ministry of Education, Division of Spine Surgery, Department of Orthopedics, 
      Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, 
      China.
FAU - Cheng, Li-Ming
AU  - Cheng LM
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the 
      Ministry of Education, Division of Spine Surgery, Department of Orthopedics, 
      Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20211125
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC8657151
OTO - NOTNLM
OT  - BKCa channel
OT  - MAPKs phosphorylation
OT  - TNF-alpha
OT  - trigeminal neuralgia
OT  - trigeminal nucleus caudalis
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- 2021/12/14 06:00
MHDA- 2021/12/14 06:01
PMCR- 2021/01/01
CRDT- 2021/12/13 17:52
PHST- 2021/08/25 00:00 [received]
PHST- 2021/10/18 00:00 [accepted]
PHST- 2021/12/13 17:52 [entrez]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2021/12/14 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2021.764141 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2021 Nov 25;15:764141. doi: 10.3389/fncel.2021.764141. 
      eCollection 2021.