PMID- 34324688
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1938-5404 (Electronic)
IS  - 0033-7587 (Linking)
VI  - 196
IP  - 4
DP  - 2021 Oct 1
TI  - Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of 
      Transient Receptor Potential (TRP) Ion Channels.
PG  - 331-344
LID - 10.1667/RADE-21-000103.1 [doi]
AB  - Signal transduction at sensory neurons occurs via transmembrane flux of cations, 
      which is largely governed by the transient receptor potential (TRP) family of ion 
      channels. It is unknown whether TRP channel activation contributes to the pain 
      that accompanies radiation-induced oral mucositis. This study sought to 
      characterize changes in TRP channel expression and function that occur in the 
      locally irradiated tissues and afferent neurons of mice. Female CD-1 mice 
      received single high-dose (27 Gy) tongue irradiation, or sham irradiation. 
      Animals were euthanized either before overt glossitis developed (days 1 and 5 
      postirradiation), when glossitis was severe (day 11), or after mice had recovered 
      (days 21 and 45). Tongue irradiation caused upregulation of the Trpv1 gene in 
      trigeminal ganglia (TG) neurons. Other TRP genes (Trpv2, Trpv4, Trpa1, Trpm8) and 
      Gfralpha3 (which acts upstream of several TRP channels) were also upregulated in TGs 
      and/or tongue tissue, in response to radiation. Ex vivo calcium imaging 
      experiments demonstrated that the proportions of TG neurons responding to 
      histamine (an activator of TRPV1, TRPV4 and TRPA1), TNF-alpha (an activator of TRPV1, 
      TRPV2 and TRPV4), and capsaicin (a TRPV1 agonist), were increased as early as one 
      day after tongue irradiation; these changes persisted for at least 21 days. In a 
      subsequent experiment, we found that genetic deletion of TRPV1 mitigated weight 
      loss (a surrogate marker of pain severity) in mice with severe glossitis. The 
      results intimate that various TRP channels, and TRPV1 in particular, should be 
      explored as analgesic targets for patients experiencing pain after oral 
      irradiation.
CI  - (c)2021 by Radiation Research Society. All rights of reproduction in any form 
      reserved.
FAU - Lai, Yen
AU  - Lai Y
AD  - Department of Clinical Sciences, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Comparative Medicine Institute, North Carolina State University, Raleigh, North 
      Carolina.
FAU - Baumer, Wolfgang
AU  - Baumer W
AD  - Department of Molecular Biomedical Sciences, North Carolina State University, 
      Raleigh, North Carolina.
AD  - Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, 
      Freie Universitat Berlin, Germany.
FAU - Meneses, Constanza
AU  - Meneses C
AD  - Department of Clinical Sciences, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Translational Research in Pain, North Carolina State University, Raleigh, North 
      Carolina.
FAU - Roback, Donald M
AU  - Roback DM
AD  - Department of Radiation Oncology, Rex Cancer Center, Raleigh, North Carolina.
FAU - Robertson, James B
AU  - Robertson JB
AD  - College of Veterinary Medicine, North Carolina State University, Raleigh, North 
      Carolina.
FAU - Mishra, Santosh K
AU  - Mishra SK
AD  - Comparative Medicine Institute, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Department of Molecular Biomedical Sciences, North Carolina State University, 
      Raleigh, North Carolina.
AD  - Comparative Pain Research and Education Center, North Carolina State University, 
      Raleigh, North Carolina.
FAU - Lascelles, B Duncan X
AU  - Lascelles BDX
AD  - Department of Clinical Sciences, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Comparative Medicine Institute, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Translational Research in Pain, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Comparative Pain Research and Education Center, North Carolina State University, 
      Raleigh, North Carolina.
FAU - Nolan, Michael W
AU  - Nolan MW
AD  - Department of Clinical Sciences, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Comparative Medicine Institute, North Carolina State University, Raleigh, North 
      Carolina.
AD  - Comparative Pain Research and Education Center, North Carolina State University, 
      Raleigh, North Carolina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Radiat Res
JT  - Radiation research
JID - 0401245
RN  - 0 (Transient Receptor Potential Channels)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium
MH  - Female
MH  - Mice
MH  - Neurons
MH  - *Transient Receptor Potential Channels
MH  - Trigeminal Ganglion
MH  - Up-Regulation
EDAT- 2021/07/30 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/07/29 17:34
PHST- 2021/05/14 00:00 [received]
PHST- 2021/07/15 00:00 [accepted]
PHST- 2021/07/30 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/29 17:34 [entrez]
AID - 468451 [pii]
AID - 10.1667/RADE-21-000103.1 [doi]
PST - ppublish
SO  - Radiat Res. 2021 Oct 1;196(4):331-344. doi: 10.1667/RADE-21-000103.1.