PMID- 36359772
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20221211
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 21
DP  - 2022 Oct 26
TI  - Upregulation of Na(v)1.6 Mediated by the p38 MAPK Pathway in the Dorsal Root 
      Ganglia Contributes to Cancer-Induced Bone Pain in Rats.
LID - 10.3390/cells11213375 [doi]
LID - 3375
AB  - Cancer-induced bone pain (CIBP) occurs frequently among advanced cancer patients. 
      Voltage-gated sodium channels (VGSCs) have been associated with chronic pain, but 
      how VGSCs function in CIBP is poorly understood. Here, we aimed to investigate 
      the specific role of VGSCs in the dorsal root ganglia (DRGs) in CIBP. A CIBP rat 
      model was generated by the intratibial inoculation of MRMT-1 breast carcinoma 
      cells. Transcriptome sequencing was conducted to assess the gene expression 
      profiles. The expression levels of key genes and differentiated genes related to 
      activated pathways were measured by Western blotting and qPCR. We implanted a 
      catheter intrathecally for the administration of lentivirus and drugs. Then, the 
      changes in the mechanical withdrawal threshold (MWT) were measured. We identified 
      149 differentially expressed mRNAs (DEmRNAs) in the DRGs of CIBP model rats. The 
      expression of Na(v)1.6, which was among these DEmRNAs, was significantly 
      upregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis 
      of the DEmRNAs showed that they were mainly enriched in the mitogen-activated 
      protein kinase (MAPK) pathway. The decrease in MWT induced by bone cancer was 
      attenuated by Na(v)1.6 knockdown. Western blot analysis revealed that a p38 
      inhibitor decreased the expression of Na(v)1.6 and attenuated pain behavior. Our 
      study shows that the upregulation of Na(v)1.6 expression by p38 MAPK in the DRGs 
      of rats contributes to CIBP.
FAU - Lin, Mingxue
AU  - Lin M
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Chen, Xiaohui
AU  - Chen X
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Wu, Shuyan
AU  - Wu S
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Chen, Pinzhong
AU  - Chen P
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Wan, Haiyang
AU  - Wan H
AD  - Department of Anesthesiology, First Affiliated Hospital of Yangtze University, 
      First People's Hospital of Jingzhou, Jingzhou 434000, China.
FAU - Ma, Simeng
AU  - Ma S
AD  - Fujian Provincial Maternity and Children's Hospital, Fuzhou 350000, China.
FAU - Lin, Na
AU  - Lin N
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Liao, Yanling
AU  - Liao Y
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Zheng, Ting
AU  - Zheng T
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Jiang, Jundan
AU  - Jiang J
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
FAU - Zheng, Xiaochun
AU  - Zheng X
AD  - Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical 
      University, Fujian Provincial Hospital, Fuzhou 350000, China.
AD  - Fujian Emergency Medical Center, Fujian Provincial Key Laboratory of Critical 
      Care Medicine, Fuzhou 350000, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221026
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - 0 (Voltage-Gated Sodium Channels)
RN  - 0 (Scn8a protein, rat)
RN  - 0 (NAV1.6 Voltage-Gated Sodium Channel)
SB  - IM
MH  - Animals
MH  - Rats
MH  - Bone Neoplasms/complications/metabolism
MH  - Ganglia, Spinal/metabolism
MH  - *p38 Mitogen-Activated Protein Kinases/metabolism
MH  - Pain/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation
MH  - Voltage-Gated Sodium Channels/metabolism
MH  - *NAV1.6 Voltage-Gated Sodium Channel/genetics/metabolism
MH  - *Cancer Pain/genetics/metabolism
PMC - PMC9654392
OTO - NOTNLM
OT  - MAPK pathway
OT  - Nav1.6
OT  - RNA-seq
OT  - cancer-induced bone pain
OT  - dorsal root ganglion
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/10/26
CRDT- 2022/11/11 01:12
PHST- 2022/08/28 00:00 [received]
PHST- 2022/10/19 00:00 [revised]
PHST- 2022/10/21 00:00 [accepted]
PHST- 2022/11/11 01:12 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/10/26 00:00 [pmc-release]
AID - cells11213375 [pii]
AID - cells-11-03375 [pii]
AID - 10.3390/cells11213375 [doi]
PST - epublish
SO  - Cells. 2022 Oct 26;11(21):3375. doi: 10.3390/cells11213375.