Substance P sensitizes P2X3 in nociceptive trigeminal neurons

Journal of Dental Research
Chul-Kyu ParkS B Oh

Abstract

Peripheral inflammation produces pain hypersensitivity by sensitizing nociceptors. Potentiation of P2X3 receptor activity in nociceptors may play an important role in this peripheral sensitization. However, we do not fully understand how P2X3 activity is elevated in inflammation. Thus, we investigated whether P2X3 activity in trigeminal nociceptive neurons is regulated by the neurokinin-1 (NK-1) receptor that is activated by an inflammatory mediator, substance P. Single-cell RT-PCR and immunohistochemistry revealed that NK-1 in nociceptive neurons was mainly co-expressed with P2X3. Ca(2+) imaging and whole-cell patch-clamp recordings indicated that both substance P and Sar-substance P, a selective NK-1 agonist, significantly potentiated α,β-meATP-induced currents and [Ca(2+)](i) responses in nociceptive neurons. These potentiating effects were completely blocked by GR82334, a specific NK-1 antagonist. Our results demonstrate that substance P sensitizes P2X3 receptor through the activation of NK-1, thus warranting these receptors as possible targets for pain therapy in the orofacial region. α,β-methylene adenosine 5'-triphosphate (ATP), α,β-meATP; neurokinin-1, NK-1; single-cell reverse-transcription polymerase chain-reaction, s...Continue Reading

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Citations

Apr 5, 2012·Mediators of Inflammation·Paola Sacerdote, Luca Levrini
Feb 18, 2014·The Journal of Clinical Investigation·Temugin BertaRu-Rong Ji
Apr 18, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sungjae YooSun Wook Hwang
Sep 19, 2014·International Journal of Molecular Sciences·Seung-In ChoiSun Wook Hwang
Oct 27, 2016·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Y-Q HeM Yang
Nov 29, 2014·Molecular Pain·Eder Ricardo MoraesLigia Araujo Naves
Aug 21, 2013·Journal of Dental Research·G ChungS B Oh
Nov 7, 2018·Investigative Ophthalmology & Visual Science·Barbariga MarcoFerrari Giulio
Apr 3, 2019·International Journal of Molecular Sciences·Chu-Ting ChangChih-Cheng Chen
Jan 3, 2014·Physiological Reviews·Martin S SteinhoffNigel W Bunnett
Dec 20, 2012·Molecular Pharmacology·Gary MoPhilippe Séguéla
Aug 20, 2020·European Journal of Orthodontics·Gregory S AntonarakisStavros Kiliaridis
Jan 17, 2017·Cell and Tissue Research·Katrin Julia AudritChristina Nassenstein
Sep 30, 2021·Journal of Oral Rehabilitation·Ziwei TangFan Jian

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Methods Mentioned

BETA
PCR
confocal microscopy

Software Mentioned

HEKA
Pulse
MetaMorph
Origin

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