PMID- 33853615
OWN - NLM
STAT- MEDLINE
DCOM- 20211118
LR  - 20211118
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 18
IP  - 1
DP  - 2021 Apr 14
TI  - TNF-alpha acutely enhances acid-sensing ion channel currents in rat dorsal root 
      ganglion neurons via a p38 MAPK pathway.
PG  - 92
LID - 10.1186/s12974-021-02151-w [doi]
LID - 92
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine 
      involved in pain processing and hypersensitivity. It regulates not only the 
      expression of a variety of inflammatory mediators but also the functional 
      activity of some ion channels. Acid-sensing ion channels (ASICs), as key sensors 
      for extracellular protons, are expressed in nociceptive sensory neurons and 
      contribute to pain signaling caused by tissue acidosis. It is still unclear 
      whether TNF-alpha has an effect on functional activity of ASICs. Herein, we reported 
      that a brief exposure of TNF-alpha acutely sensitized ASICs in rat dorsal root 
      ganglion (DRG) neurons. METHODS: Electrophysiological experiments on rat DRG 
      neurons were performed in vitro and acetic acid induced nociceptive behavior 
      quantified in vitro. RESULTS: A brief (5min) application of TNF-alpha rapidly 
      enhanced ASIC-mediated currents in rat DRG neurons. TNF-alpha (0.1-10 ng/ml) 
      dose-dependently increased the proton-evoked ASIC currents with an EC(50) value 
      of 0.12 +/- 0.01 nM. TNF-alpha shifted the concentration-response curve of proton 
      upwards with a maximal current response increase of 42.34 +/- 7.89%. In 
      current-clamp recording, an acute application of TNF-alpha also significantly 
      increased acid-evoked firing in rat DRG neurons. The rapid enhancement of 
      ASIC-mediated electrophysiological activity by TNF-alpha was prevented by p38 
      mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by 
      non-selective cyclooxygenase inhibitor indomethacin, suggesting that p38 MAPK is 
      necessary for this enhancement. Behaviorally, TNF-alpha exacerbated acid-induced 
      nociceptive behaviors in rats via activation of local p38 MAPK pathway. 
      CONCLUSIONS: These results suggest that TNF-alpha rapidly enhanced ASIC-mediated 
      functional activity via a p38 MAPK pathway, which revealed a novel peripheral 
      mechanism underlying TNF-alpha involvement in rapid hyperalgesia by sensitizing ASICs 
      in primary sensory neurons.
FAU - Wei, Shuang
AU  - Wei S
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, 
      Hubei, PR China.
AD  - Department of Pharmacology, Hubei University of Science and Technology, 88 
      Xianning Road, Xianning, 437100, Hubei, PR China.
FAU - Qiu, Chun-Yu
AU  - Qiu CY
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, 
      Hubei, PR China.
FAU - Jin, Ying
AU  - Jin Y
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, 
      Hubei, PR China.
FAU - Liu, Ting-Ting
AU  - Liu TT
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, 
      Hubei, PR China.
FAU - Hu, Wang-Ping
AU  - Hu WP
AUID- ORCID: 0000-0003-1870-325X
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, 
      Hubei, PR China. wangping_hu@163.com.
LA  - eng
GR  - No. 81671101/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20210414
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Acid Sensing Ion Channels)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - Q40Q9N063P (Acetic Acid)
SB  - IM
MH  - Acetic Acid/pharmacology
MH  - Acid Sensing Ion Channels/*metabolism
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Ganglia, Spinal/*cytology
MH  - Hyperalgesia/chemically induced/metabolism
MH  - Male
MH  - Neurons/*drug effects/metabolism
MH  - Nociceptors/metabolism/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sensory Receptor Cells/drug effects/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC8048296
OTO - NOTNLM
OT  - Acid-sensing ion channels
OT  - Dorsal root ganglion neuron
OT  - Electrophysiology
OT  - Nociceptive response
OT  - Tumor necrosis factor-alpha
COIS- We have no conflict-of-interest to declare.
EDAT- 2021/04/16 06:00
MHDA- 2021/11/19 06:00
PMCR- 2021/04/14
CRDT- 2021/04/15 05:43
PHST- 2021/02/15 00:00 [received]
PHST- 2021/04/07 00:00 [accepted]
PHST- 2021/04/15 05:43 [entrez]
PHST- 2021/04/16 06:00 [pubmed]
PHST- 2021/11/19 06:00 [medline]
PHST- 2021/04/14 00:00 [pmc-release]
AID - 10.1186/s12974-021-02151-w [pii]
AID - 2151 [pii]
AID - 10.1186/s12974-021-02151-w [doi]
PST - epublish
SO  - J Neuroinflammation. 2021 Apr 14;18(1):92. doi: 10.1186/s12974-021-02151-w.