Superoxide signaling in pain is independent of nitric oxide signaling

Two reactive oxygen species (ROS), nitric oxide (NO center dot) and superoxide (O-center dot(2)-), contribute to persistent pain. Using three different animal models where ROS mediate pain, this study examined whether NO center dot and O-center dot(2)- converge to peroxynitrite (ONOO-) or whether each has an independent signaling pathway to produce hyperalgesia. The hyperalgesia after spinal nerve ligation was attenuated by removing O-center dot(2)- by TEMPOL or inhibiting NO center dot production by L-NAME, but not by removing peroxynitrite with FeTMPyP. Nitric oxide-induced hyperalgesia was not affected by removing O-center dot(2)- but was reduced by a guanyl cyclase inhibitor. Superoxide-induced hyperalgesia was not affected by inhibiting NO center dot production but was suppressed by a protein kinase C inhibitor. The data suggest that NO center dot and O-center dot(2)- operate independently to generate pain. NeuroReport 20:1424-1428 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.