PMID- 34234509
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - Acute P38-Mediated Enhancement of P2X3 Receptor Currents by TNF-alpha in Rat Dorsal 
      Root Ganglion Neurons.
PG  - 2841-2850
LID - 10.2147/JIR.S315774 [doi]
AB  - PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine and 
      involves in a variety of pain conditions. Some findings suggest that TNF-alpha may 
      act directly on primary afferent neurons to induce acute pain hypersensitivity 
      through non-transcriptional regulation. This study investigated whether TNF-alpha had 
      an effect on functional activity of P2X3 receptors in primary sensory neurons. 
      Herein, we report that a brief (5 min) application of TNF-alpha rapidly enhanced the 
      electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) 
      neurons. METHODS: Electrophysiological recordings were carried out on rat DRG 
      neurons, and nociceptive behavior was quantified in rats. RESULTS: A brief (5 
      min) exposure of TNF-alpha rapidly increased P2X3 receptor-mediated and 
      alpha,beta-methylene-ATP (alpha,beta-meATP)-evoked inward currents in a dose-dependent manner. 
      The potentiation of P2X3 receptor-mediated ATP currents by TNF-alpha was 
      voltage-independent. TNF-alpha shifted the concentration-response curve for alpha,beta-meATP 
      upwards, with an increase of 31.57 +/- 6.81% in the maximal current response to 
      alpha,beta-meATP. This acute potentiation of ATP currents by TNF-alpha was blocked by p38 
      mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by 
      non-selective cyclooxygenase inhibitor indomethacin, suggesting involvement of 
      p38 MAPK, but not cyclooxygenase. Moreover, intraplantar injection of TNF-alpha and 
      alpha,beta-meATP produced a synergistic effect on mechanical allodynia in rats. 
      TNF-alpha-induced mechanical allodynia was also alleviated after local P2X3 receptors 
      were blocked. CONCLUSION: These results suggested that TNF-alpha rapidly sensitized 
      P2X3 receptors in primary sensory neurons via a p38 MAPK dependent pathway, which 
      revealed a novel peripheral mechanism underlying acute mechanical 
      hypersensitivity by peripheral administration of TNF-alpha.
CI  - (c) 2021 Jin et al.
FAU - Jin, Ying
AU  - Jin Y
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, Xianning, Hubei, 437100, People's 
      Republic of China.
FAU - Wei, Shuang
AU  - Wei S
AD  - Research Center of Basic Medical Sciences, School of Basic Medical Sciences, 
      Hubei University of Science and Technology, Xianning, Hubei, 437100, People's 
      Republic of 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, Xianning, Hubei, 437100, People's 
      Republic of 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, Xianning, Hubei, 437100, People's 
      Republic of 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, Xianning, Hubei, 437100, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210629
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8254564
OTO - NOTNLM
OT  - P2X3 receptor
OT  - dorsal root ganglion neuron
OT  - electrophysiology
OT  - nociceptive response
OT  - tumor necrosis factor-alpha
COIS- The authors have no conflict of interest to declare.
EDAT- 2021/07/09 06:00
MHDA- 2021/07/09 06:01
PMCR- 2021/06/29
CRDT- 2021/07/08 06:37
PHST- 2021/04/22 00:00 [received]
PHST- 2021/06/05 00:00 [accepted]
PHST- 2021/07/08 06:37 [entrez]
PHST- 2021/07/09 06:00 [pubmed]
PHST- 2021/07/09 06:01 [medline]
PHST- 2021/06/29 00:00 [pmc-release]
AID - 315774 [pii]
AID - 10.2147/JIR.S315774 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Jun 29;14:2841-2850. doi: 10.2147/JIR.S315774. eCollection 
      2021.