SOD2/MnSOD is the major SO-scavenging enzyme expressed in the mitochondria, and its selective knockout in the brain results in a lethal phenotype.[[68], [123]] SOD1/CuZnSOD is predominantly expressed in the cytosol, whereas SOD3/CuZnSOD is responsible for extracellular SO scavenging.[168] Other sources of SO include the catabolism of purine nucleic acids by xanthine oxidase (XO)[2] and the activity of the membrane-bound NADPH oxidase family (NOX1-5 and DUOX1-2).[126] The existence of specific SOD isoforms underlines the importance of a tight control of SO/H SB 2 sb O SB 2 sb levels in different cellular compartments to regulate diverse physiological functions. Pathological pain states arising from injuries to the nervous system are characterized by sustained neuroinflammation and increased neuronal excitability at both peripheral and central level.[[108], [162]] Overproduction of reactive oxygen and nitrogen (nitroxidative) species, such as superoxide (SO) and peroxynitrite (PN, ONOO SP - sp ), and impaired endogenous antioxidant defenses play critical roles in triggering chronic pain states.[[136], [140]] In particular, a growing body of evidence indicates a major involvement of SO and PN in inflammatory and neuropathic pain states as well as in the development of increased pain sensitivity during prolonged opioid use (opioid-induced hyperalgesia). 165 Wang H,, Song T,, Wang W,, Zhang Z. TRPM2 participates the transformation of acute pain to chronic pain during injury-induced neuropathic pain. [Extracted from the article]