Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical secondary hyperalgesia in mice

Recent studies indicate that reactive oxygen species (ROS) are critically involved ill persistent pain primarily through spinal mechanisms. thus suggesting ROS involvement ill central sensitization. To investigate ROS involvement ill central sensitization, the effects of ROS scavengers and donors oil pain behaviors were examined ill mice. Capsaicin-induced hyperalgesia was used as it pain model since it has 2 distinctive Pain components. Primary and secondary hyperalgesia representing peripheral and central sensitization. respectively. Capsaicin (25 mu g/5 mu l) was injected intradermally into the left hind loot. Foot withdrawal frequencies ill response to von Frey filament stimuli were measured and used as an indicator of mechanical hyperalgesia. The production of ROS was examined by using ROS sensitive dye, MitoSox. Mice developed primary and secondary mechanical hyperalgesia after capsaicin injection. A systemic or intrathecal post-treatment with either phenyl-N-tert-butylnitrone (PBN) or 4-hydroxy-2.2,6,6-tetramethylpiperidine-1 oxyl (TEMPOL), ROS scavengers, significantly reduced secondary hyperalgesia, but not primary hyperalgesia, in a dose-dependent manner. Pretreatment with ROS scavengers also significantly reduced the magnitude and duration of capsaicin-induced secondary hyperalgesia. On the other hand, intrathecal injection of tert-butylhydroperoxide (t-BOOH, 5 mu l), a ROS donor, produced a transient hyperalgesia in a dose-dependent manner. The number of MitoSox positive dorsal horn neurons was increased significantly after capsaicin treatment. This study suggests that ROS mediates the development and maintenance of capsaicin- induced hyperalgesia in mice, mainly through central sensitization and that the elevation of spinal ROS is most likely due to increased production of mitochondrial superoxides in the dorsal horn neurons. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.