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

Trends Neurosci. 2016 Dec;39(12):862-879. doi: 10.1016/j.tins.2016.10.003. Epub 2016 Nov 12.

Authors

Peter M Grace¹, Andrew D Gaudet², Vasiliki Staikopoulos³, Steven F Maier², Mark R Hutchinson³, Daniela Salvemini⁴, Linda R Watkins²

Affiliations

¹ 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.
² Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO, USA.
³ Discipline of Physiology, School of Medicine, and the Australian Research Council (ARC) Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide, Adelaide, SA, Australia.
⁴ Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.

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.

Keywords: NADPH oxidase; TRP channels; exercise; mitochondria; neuroinflammation; sensitization.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Animals
Humans
Mitochondria / metabolism
NADPH Oxidases / metabolism*
Neurons / metabolism
Pain / metabolism*
Reactive Nitrogen Species / metabolism*
Reactive Oxygen Species / metabolism*
Signal Transduction

Substances

Reactive Nitrogen Species
Reactive Oxygen Species
NADPH Oxidases

Grants and funding

R01 DE021966/DE/NIDCR NIH HHS/United States