Oxidative stress due to overproduction of reactive oxygen species (ROS) may impair normal cellular processes and ultimately result in cellular death. Previously, we found that ROS is significantly involved in the generation and maintenance of neuropathic pain in the spinal nerve ligation (SNL) model in the rat. To be able to utilize genetically manipulated animals to uncover the mechanism underlying ROS's role in pain, we initiated the study of ROS involvement in neuropathic pain in mice. SNL mice were produced by tight ligation of the L5 spinal nerve in FVB/NJ adult male mice. Development of pain behavior was confirmed through the frequency of paw withdrawal responses to von Frey stimuli #3.0 (0.1g) and #3.61 (0.41g) to assess mechanical allodynia. At one, two and three weeks post SNL, the effects of systemic administration of ROS scavenger phenyl-N-tert-butylnitrone (PBN) at 150mg/kg (i.p.) on pain behavior was tested. Intrathecal injection of PBN at 200ug/5ul (i.t.) was performed one week after SNL. Mechanical sensitivity, measured as frequency responses to von Frey stimuli, were consistently increased to 70%-100% in the majority of SNL mice compared to 0-10% in normal. The time course of pain behavior lasts roughly eight weeks. PBN (150mg/kg i.p.) temporarily reversed mechanical allodynia for 2 hours one week after SNL. This effect was maintained at least 3 weeks. Intrathecal PBN (200ug/5ul) more robustly decreased mechanical allodynia with a similar time course. These data show that SNL produces neuropathic pain in the mouse. Systemic or intrathecal PBN has analgesic effects in the SNL model in mice. Intrathecal data suggest PBN acts primarily in the spinal cord. The results suggest that ROS play an important role in neuropathic pain in mice. (Supported by NIH Grants NS31680 and NS11255)