PMID- 29696511
OWN - NLM
STAT- MEDLINE
DCOM- 20190401
LR  - 20200225
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 1
DP  - 2019 Jan
TI  - TNFalpha in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint 
      Pain.
PG  - 278-291
LID - 10.1007/s12035-018-1076-y [doi]
AB  - Previous studies have shown that tumor necrosis factor alpha (TNFalpha) is 
      significantly increased in complete Freund's adjuvant (CFA)-treated 
      temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFalpha in the 
      trigeminal nociceptive system contributes to the development of TMJ pain. In the 
      present study, we investigated the role of TNFalpha in trigeminal ganglia (TG) and 
      spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. 
      Intra-TMJ injection of CFA (10 mul, 5 mg/ml) induced inflammatory pain in the 
      trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present 
      on day 1 after CFA and persisted for at least 10 days. TNFalpha in both TG and Sp5C 
      of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was 
      significantly inhibited in TNFalpha KO mice. The immunofluorescence staining showed 
      that intra-TMJ CFA injection not only enhanced co-localization of TNFalpha with Iba1 
      (a marker for microglia) in both TG and Sp5C but also markedly increased the 
      expression of TNFalpha in the Sp5C neurons. By the methylated DNA immunoprecipitation 
      assay, we also found that DNA methylation at the TNF gene promoter region in the 
      TG was dramatically diminished after CFA injection, indicating that epigenetic 
      regulation may be involved in the CFA-enhanced TNFalpha expression in our model. Our 
      results suggest that TNFalpha in the trigeminal nociceptive system plays a critical 
      role in CFA-induced inflammatory TMJ pain.
FAU - Bai, Qian
AU  - Bai Q
AD  - Department of Anesthesiology, The Second Affiliated Hospital at Zhengzhou 
      University School of Medicine, 2 Jingba Rd, Zhengzhou, 450000, Henan, China.
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA.
FAU - Liu, Sufang
AU  - Liu S
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA.
AD  - Department of Physiology and Neurobiology, Zhengzhou University School of 
      Medicine, Zhengzhou, Henan, China.
FAU - Shu, Hui
AU  - Shu H
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA.
FAU - Tang, Yuanyuan
AU  - Tang Y
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA.
AD  - School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 
      China.
FAU - George, Sanjeeth
AU  - George S
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA.
FAU - Dong, Tieli
AU  - Dong T
AD  - Department of Anesthesiology, The Second Affiliated Hospital at Zhengzhou 
      University School of Medicine, 2 Jingba Rd, Zhengzhou, 450000, Henan, China. 
      tlddtl@126.com.
FAU - Schmidt, Brian L
AU  - Schmidt BL
AD  - Bluestone Center for Clinical Research, New York University, New York, NY, USA.
FAU - Tao, Feng
AU  - Tao F
AUID- ORCID: 0000-0002-0623-6298
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, Texas, USA. tao@tamhsc.edu.
AD  - Center for Craniofacial Research and Diagnosis, Texas A&M University College of 
      Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA. tao@tamhsc.edu.
LA  - eng
GR  - K02 DE023551/DE/NIDCR NIH HHS/United States
GR  - R01 DE022880/DE/NIDCR NIH HHS/United States
PT  - Journal Article
DEP - 20180425
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Methylation
MH  - Freund's Adjuvant
MH  - Gene Deletion
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pain/*metabolism/*pathology
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Temporomandibular Joint/*metabolism/*pathology/physiopathology
MH  - Trigeminal Ganglion/*metabolism/*pathology
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
MH  - Up-Regulation
PMC - PMC6698364
MID - NIHMS1044841
OTO - NOTNLM
OT  - Inflammatory pain
OT  - Spinal trigeminal nucleus caudalis
OT  - Temporomandibular joint
OT  - Trigeminal ganglia
OT  - Tumor necrosis factor-alpha
COIS- Conflict of Interest The authors have no conflicts of interest to declare.
EDAT- 2018/04/27 06:00
MHDA- 2019/04/02 06:00
PMCR- 2020/01/01
CRDT- 2018/04/27 06:00
PHST- 2018/01/03 00:00 [received]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2019/04/02 06:00 [medline]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.1007/s12035-018-1076-y [pii]
AID - 10.1007/s12035-018-1076-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Jan;56(1):278-291. doi: 10.1007/s12035-018-1076-y. Epub 2018 
      Apr 25.