The Contribution of Nitroxidative Stress to Pathophysiological Pain and Opioid Analgesic Failure View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2016

AUTHORS

Ashley M. Symons-Liguori , Kali Janes , William L. Neumann , Daniela Salvemini

ABSTRACT

Chronic pain affects nearly 10 % of the population worldwide and poses a tremendous socioeconomic burden. Current therapeutic strategies, which range from nonsteroidal anti-inflammatory drugs (NSAIDs) to powerful opioids like morphine and fentanyl, do not effectively manage chronic pain in the majority of patients. A better understanding of pathophysiological nociception and the therapeutic targets therein is necessary. The generation of nitroxidative (nitrative and oxidative) stress—that is, the formation of superoxide and nitric oxide in tandem, their subsequent reaction to afford peroxynitrite, and the reaction of peroxynitrite and its decomposition products with biological molecules—is clearly involved in various types of persistent pain. In this chapter, we will catalogue the mechanistic pharmacological studies that support the contribution of nitroxidative stress to chronic pain, identify the cellular and enzymatic sources of nitroxidative species involved in this pathology, and delineate the mechanisms by which nitroxidative stress impacts nociceptive processing to produce persistent pain. Specifically, we will highlight the contribution of peroxynitrite (e.g., through nitration chemistry) to enhanced pro-nociceptive neurotransmission (modifications of glutamatergic, vanilloid, and prostaglandin signaling), suppressed inhibitory neurotransmission (modifications of GABAergic and catecholamine signaling), and to changes in transcriptional regulation that underpin chronic pain. Our overall goal is to refine the current generalized understanding of roles of reactive oxygen and nitrogen species in persistent pain by defining nitroxidative stress as a specific, targetable pro-nociceptive mechanism for the ultimate treatment of chronic pain. More... »

PAGES

563-595

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  • Book

    TITLE

    Redox-Active Therapeutics

    ISBN

    978-3-319-30703-9
    978-3-319-30705-3

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/978-3-319-30705-3_25

    DOI

    http://dx.doi.org/10.1007/978-3-319-30705-3_25

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002765661


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