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Nitroxidative Signaling Mechanisms in Pathological Pain
Open accessAbstract
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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“This is because the mechanisms that cause pathological pain and those that cause exercise-induced muscle pain are different from each other [41,42].”
From Acute effects of brief mindfulness intervention coupled with carbohydrate ingestion to re-energize soccer players: a randomized crossover trial. (2020) · cites this paper as [41]
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Metadata
- 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
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 39
- Issue
- 12
- Pages
- 862-879
- ISSN
- 0166-2236 (ISSN-L)
- 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
- 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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