Nitroxidative Signaling Mechanisms in Pathological Pain

Peter M. Grace; Andrew D. Gaudet; Vasiliki Staikopoulos; Steven F. Maier; Mark R. Hutchinson; Daniela Salvemini; Linda R. Watkins

doi:10.1016/j.tins.2016.10.003

Nitroxidative Signaling Mechanisms in Pathological Pain

Peter M. Grace, Andrew D. Gaudet, Vasiliki Staikopoulos, Steven F. Maier, Mark R. Hutchinson, Daniela Salvemini, Linda R. Watkins

Critical Care & Respiratory Care

Research output: Contribution to journal › Review article › peer-review

89 Scopus citations

Abstract

Tissue injury can initiate bidirectional signaling between neurons, glia, and immune cells that creates and amplifies pain. While the ability for neurotransmitters, neuropeptides, and cytokines to initiate and maintain pain has been extensively studied, recent work has identified a key role for reactive oxygen and nitrogen species (ROS/RNS; nitroxidative species), including superoxide, peroxynitrite, and hydrogen peroxide. In this review we describe how nitroxidative species are generated after tissue injury and the mechanisms by which they enhance neuroexcitability in pain pathways. Finally, we discuss potential therapeutic strategies for normalizing nitroxidative signaling, which may also enhance opioid analgesia, to help to alleviate the enormous burden of pathological pain.

Original language	English (US)
Pages (from-to)	862-879
Number of pages	18
Journal	Trends in Neurosciences
Volume	39
Issue number	12
DOIs	https://doi.org/10.1016/j.tins.2016.10.003
State	Published - Dec 1 2016

Keywords

NADPH oxidase
TRP channels
exercise
mitochondria
neuroinflammation
sensitization

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.tins.2016.10.003

Cite this

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title = "Nitroxidative Signaling Mechanisms in Pathological Pain",

abstract = "Tissue injury can initiate bidirectional signaling between neurons, glia, and immune cells that creates and amplifies pain. While the ability for neurotransmitters, neuropeptides, and cytokines to initiate and maintain pain has been extensively studied, recent work has identified a key role for reactive oxygen and nitrogen species (ROS/RNS; nitroxidative species), including superoxide, peroxynitrite, and hydrogen peroxide. In this review we describe how nitroxidative species are generated after tissue injury and the mechanisms by which they enhance neuroexcitability in pain pathways. Finally, we discuss potential therapeutic strategies for normalizing nitroxidative signaling, which may also enhance opioid analgesia, to help to alleviate the enormous burden of pathological pain.",

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T1 - Nitroxidative Signaling Mechanisms in Pathological Pain

AU - Grace, Peter M.

AU - Gaudet, Andrew D.

AU - Staikopoulos, Vasiliki

AU - Maier, Steven F.

AU - Hutchinson, Mark R.

AU - Salvemini, Daniela

AU - Watkins, Linda R.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Tissue injury can initiate bidirectional signaling between neurons, glia, and immune cells that creates and amplifies pain. While the ability for neurotransmitters, neuropeptides, and cytokines to initiate and maintain pain has been extensively studied, recent work has identified a key role for reactive oxygen and nitrogen species (ROS/RNS; nitroxidative species), including superoxide, peroxynitrite, and hydrogen peroxide. In this review we describe how nitroxidative species are generated after tissue injury and the mechanisms by which they enhance neuroexcitability in pain pathways. Finally, we discuss potential therapeutic strategies for normalizing nitroxidative signaling, which may also enhance opioid analgesia, to help to alleviate the enormous burden of pathological pain.

AB - Tissue injury can initiate bidirectional signaling between neurons, glia, and immune cells that creates and amplifies pain. While the ability for neurotransmitters, neuropeptides, and cytokines to initiate and maintain pain has been extensively studied, recent work has identified a key role for reactive oxygen and nitrogen species (ROS/RNS; nitroxidative species), including superoxide, peroxynitrite, and hydrogen peroxide. In this review we describe how nitroxidative species are generated after tissue injury and the mechanisms by which they enhance neuroexcitability in pain pathways. Finally, we discuss potential therapeutic strategies for normalizing nitroxidative signaling, which may also enhance opioid analgesia, to help to alleviate the enormous burden of pathological pain.

KW - NADPH oxidase

KW - TRP channels

KW - exercise

KW - mitochondria

KW - neuroinflammation

KW - sensitization

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Nitroxidative Signaling Mechanisms in Pathological Pain

Abstract

Keywords

ASJC Scopus subject areas

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