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.
Peter M Grace, Andrew D Gaudet, Vasiliki Staikopoulos, Steven F Maier, Mark R Hutchinson, Daniela Salvemini, and Linda R Watkins.
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 ... more Cancer Center, Houston, TX, USA. Electronic address: pgrace@mdanderson.org. less