PMID- 33215551
OWN - NLM
STAT- MEDLINE
DCOM- 20210805
LR  - 20210805
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 16
DP  - 2020 Jan-Dec
TI  - Orthodontic force induces nerve injury-like transcriptomic changes driven by 
      TRPV1-expressing afferents in mouse trigeminal ganglia.
PG  - 1744806920973141
LID - 10.1177/1744806920973141 [doi]
LID - 1744806920973141
AB  - Orthodontic force produces mechanical irritation and localized inflammation in 
      the periodontium, which causes pain in most patients. Nocifensive behaviors 
      resulting from orthodontic force in mice can be substantially attenuated by 
      intraganglionic injection of resiniferatoxin (RTX), a neurotoxin that 
      specifically ablates a subset of neurons expressing transient receptor potential 
      vanilloid 1 (TRPV1). In the current study, we determined changes in the 
      transcriptomic profiles in the trigeminal ganglia (TG) following the application 
      of orthodontic force, and assessed the roles of TRPV1-expressing afferents in 
      these transcriptomic changes. RTX or vehicle was injected into the TG of mice a 
      week before the placement of an orthodontic spring exerting 10 g of force. After 
      2 days, the TG were collected for RNA sequencing. The application of orthodontic 
      force resulted in 1279 differentially expressed genes (DEGs) in the TG. Gene 
      ontology analysis showed downregulation of gliogenesis and ion channel 
      activities, especially of voltage-gated potassium channels. DEGs produced by 
      orthodontic force correlated more strongly with DEGs resulting from nerve injury 
      than from inflammation. Orthodontic force resulted in the differential expression 
      of multiple genes involved in pain regulation, including upregulation of Atf3, 
      Adcyap1, Bdnf, and Csf1, and downregulation of Scn10a, Kcna2, Kcnj10, and P2ry1. 
      Orthodontic force-induced DEGs correlated with DEGs specific to multiple neuronal 
      and non-neuronal subtypes following nerve injury. These transcriptomic changes 
      were abolished in the mice that received the RTX injection. These results suggest 
      that orthodontic force produces transcriptomic changes resembling nerve injury in 
      the TG and that nociceptive inputs through TRPV1-expressing afferents leads to 
      subsequent changes in gene expression not only in TRPV1-positive neurons, but 
      also in TRPV1-negative neurons and non-neuronal cells throughout the ganglia. 
      Orthodontic force-induced transcriptomic changes might be an active regenerative 
      program of trigeminal ganglia in response to axonal injury following orthodontic 
      force.
FAU - Wang, Sheng
AU  - Wang S
AD  - Department of Neural and Pain Sciences, Center to Advance Chronic Pain Research, 
      University of Maryland Dental School, Baltimore, MD, USA.
FAU - Chung, Man-Kyo
AU  - Chung MK
AUID- ORCID: 0000-0001-7637-1148
AD  - Department of Neural and Pain Sciences, Center to Advance Chronic Pain Research, 
      University of Maryland Dental School, Baltimore, MD, USA.
LA  - eng
GR  - R01 DE023846/DE/NIDCR NIH HHS/United States
GR  - R01 DE027731/DE/NIDCR NIH HHS/United States
GR  - R35 DE030045/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Diterpenes)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 receptor)
RN  - A5O6P1UL4I (resiniferatoxin)
SB  - IM
MH  - Animals
MH  - Diterpenes
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Hyperalgesia/complications/genetics
MH  - Inflammation/complications/genetics/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue/*injuries/pathology
MH  - Neurons/metabolism/pathology
MH  - *Orthodontics
MH  - Reproducibility of Results
MH  - TRPV Cation Channels/*metabolism
MH  - Transcriptome/*genetics
MH  - Trigeminal Ganglion/*metabolism
PMC - PMC7686596
OTO - NOTNLM
OT  - Orthodontic pain
OT  - RNA sequencing
OT  - resiniferatoxin
OT  - trigeminal ganglia
OT  - trpv1
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/11/21 06:00
MHDA- 2021/08/06 06:00
PMCR- 2020/11/20
CRDT- 2020/11/20 08:39
PHST- 2020/11/20 08:39 [entrez]
PHST- 2020/11/21 06:00 [pubmed]
PHST- 2021/08/06 06:00 [medline]
PHST- 2020/11/20 00:00 [pmc-release]
AID - 10.1177_1744806920973141 [pii]
AID - 10.1177/1744806920973141 [doi]
PST - ppublish
SO  - Mol Pain. 2020 Jan-Dec;16:1744806920973141. doi: 10.1177/1744806920973141.