Superoxide signaling in pain is independent of nitric oxide signaling.

Abstract

Two reactive oxygen species (ROS), nitric oxide (NO(.)) and superoxide ((.)O2), contribute to persistent pain. Using three different animal models where ROS mediate pain, this study examined whether NO(.) and (.)O2 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 (.)O2 by TEMPOL or inhibiting NO(.) production by L-NAME, but not by removing peroxynitrite with FeTMPyP. Nitric oxide-induced hyperalgesia was not affected by removing (.)O2 but was reduced by a guanyl cyclase inhibitor. Superoxide-induced hyperalgesia was not affected by inhibiting NO(.) production but was suppressed by a protein kinase C inhibitor. The data suggest that NO(.) and (.)O2 operate independently to generate pain.