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 J), 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). This topical review will focus on some key observations that led to these findings and the therapeutic strategies developed to target SO and PN formation.