Pharmacology & therapeutics
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Chronic pain affects millions of people and often causes major health problems. Accumulating evidence indicates that the production of reactive oxygen species (ROS), such as superoxide anion or hydrogen peroxide, is increased in the nociceptive system during chronic inflammatory and neuropathic pain, and that ROS can act as specific signaling molecules in pain processing. Reduction of ROS levels by administration of scavengers or antioxidant compounds attenuated the nociceptive behavior in various animal models of chronic pain. ⋯ Accordingly, targeting Nox1, Nox2, and Nox4 could be a novel strategy for the treatment of chronic pain. Currently selective inhibitors of Nox enzymes are being developed. Here, we introduce the distinct roles of Nox enzymes in pain processing, we summarize recent findings in the understanding of ROS-dependent signaling pathways in the nociceptive system, and we discuss potential analgesic properties of currently available Nox inhibitors.