Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen spec...

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Autores principales:	Frances M. Munoz, Ruby Gao, Yuzhen Tian, Brian A. Henstenburg, James E. Barrett, Huijuan Hu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e7fa1811f9241d196231637c0a5d104
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spelling	oai:doaj.org-article:0e7fa1811f9241d196231637c0a5d1042021-12-02T12:30:27ZNeuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice10.1038/s41598-017-03813-72045-2322https://doaj.org/article/0e7fa1811f9241d196231637c0a5d1042017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03813-7https://doaj.org/toc/2045-2322ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R–induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079. A similar effect was observed with a P2X7R agonist, BzATP, and was attenuated by a NADPH oxidase inhibitor apocynin. Intrathecal administration of BzATP resulted in ROS production in the spinal cord and oxidative DNA damage in dorsal horn neurons. BzATP also induced robust biphasic spontaneous nociceptive behavior. Pre-treatment with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-dependently attenuated the secondary response. Here, we provide evidence that neuronal P2X7R activation leads to ROS production and subsequent nociceptive pain in mice. Together, the data indicate that P2X7R-induced ROS play a critical role in the P2X7R signaling pathway of the CNS.Frances M. MunozRuby GaoYuzhen TianBrian A. HenstenburgJames E. BarrettHuijuan HuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Frances M. Munoz Ruby Gao Yuzhen Tian Brian A. Henstenburg James E. Barrett Huijuan Hu Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
description	ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R–induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079. A similar effect was observed with a P2X7R agonist, BzATP, and was attenuated by a NADPH oxidase inhibitor apocynin. Intrathecal administration of BzATP resulted in ROS production in the spinal cord and oxidative DNA damage in dorsal horn neurons. BzATP also induced robust biphasic spontaneous nociceptive behavior. Pre-treatment with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-dependently attenuated the secondary response. Here, we provide evidence that neuronal P2X7R activation leads to ROS production and subsequent nociceptive pain in mice. Together, the data indicate that P2X7R-induced ROS play a critical role in the P2X7R signaling pathway of the CNS.
format	article
author	Frances M. Munoz Ruby Gao Yuzhen Tian Brian A. Henstenburg James E. Barrett Huijuan Hu
author_facet	Frances M. Munoz Ruby Gao Yuzhen Tian Brian A. Henstenburg James E. Barrett Huijuan Hu
author_sort	Frances M. Munoz
title	Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
title_short	Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
title_full	Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
title_fullStr	Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
title_full_unstemmed	Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
title_sort	neuronal p2x7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0e7fa1811f9241d196231637c0a5d104
work_keys_str_mv	AT francesmmunoz neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice AT rubygao neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice AT yuzhentian neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice AT brianahenstenburg neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice AT jamesebarrett neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice AT huijuanhu neuronalp2x7receptorinducedreactiveoxygenspeciesproductioncontributestonociceptivebehaviorinmice
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Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

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