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.
authors.affiliation: Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO, USA; Current address: Department of Critical Care Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: pgrace@mdanderson.org.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Grace
authors.affiliation: Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gaudet
authors.affiliation: Discipline of Physiology, School of Medicine, and the Australian Research Council (ARC) Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide, Adelaide, SA, Australia.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Staikopoulos
authors.affiliation: Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
authors.affiliation: Discipline of Physiology, School of Medicine, and the Australian Research Council (ARC) Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide, Adelaide, SA, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hutchinson
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salvemini
authors.affiliation: Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: NADPH oxidase; TRP channels; exercise; mitochondria; neuroinflammation; sensitization