Cited by 128Pain Mechanisms and TreatmentsRedox biology and oxidative stressIon Channels and Receptors

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Nitroxidative Signaling Mechanisms in Pathological Pain

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Grace, Peter M., Gaudet, Andrew D., Staikopoulos, Vasiliki, Maier, Steven F., Hutchinson, Mark R., Salvemini, Daniela, Watkins, Linda R.·2016·Trends in Neurosciences

DOI 10.1016/j.tins.2016.10.003PMC PMC5148691

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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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Authors: Grace, P. M., Gaudet, A. D., Staikopoulos, V., Maier, S. F., Hutchinson, M. R., Salvemini, D., & Watkins, L. R.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
University of Colorado Boulder (US)
Australian Research Council (AU)
Saint Louis University (US)
Corresponding author: Grace, Peter M.
ORCID: Grace, Peter M.
Gaudet, Andrew D.
Maier, Steven F.
Hutchinson, Mark R.
Salvemini, Daniela
Watkins, Linda R.
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 2016-12
Volume: 39
Issue: 12
Pages: 862-879
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/j.tins.2016.10.003
PMC: PMC5148691
OpenAlex: W2551668281
Cited by: 128
References: 218
Citations by year: 2026: 18 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 14 · 2021: 22 · 2020: 21 · 2019: 10 · 2018: 10 · 2017: 4 · 2016: 1
FWCI: 0.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders: National Institute of Dental and Craniofacial Research (R01DE021966)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: pathological pain, reactive oxygen species, reactive nitrogen species, peroxynitrite, superoxide, hydrogen peroxide, tissue damage, neuroinflammation, neuronal excitability, pain pathways, opioid analgesia, treatment options
MeSH terms: Animals, Humans, Mitochondria, Neurons, Pain, Signal Transduction, Reactive Oxygen Species, NADPH Oxidases, Reactive Nitrogen Species

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Nitroxidative Signaling Mechanisms in Pathological Pain

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