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Description:
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Recent studies indicate that reactive oxygen species (ROS ) are critically involved in persistent pain primarily through spinal mechanisms , thus suggesting ROS involvement in central sensitization . To investigate ROS involvement in central sensitization , the effects of ROS scavengers and donors on pain behaviors were examined in mice . The capsaicin -induced hyperalgesia was used as a pain model since it has 2 distinctive pain components , primary and secondary hyperalgesia representing peripheral and central sensitization , respectively . Foot withdrawal frequencies in response to von Frey filament stimuli were measured and used as an indicator of mechanical hyperalgesia . The production of mitochondrial ROS was examined by using a ROS sensitive dye MitoSox -Red . Mice developed primary and secondary mechanical hyperalgesia after capsaicin injection . A systemic or intrathecal ROS scavenger treatment significantly reduced secondary hyperalgesia , but not primary hyperalgesia , in a dose dependent manner . MitoSox positive dorsal horn neuron numbers were 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 the elevation of spinal ROS is most likely due to increased production of mitochondrial superoxides in dorsal horn neurons .
This study also investigated the role of mitochondrial antioxidant SOD2 in pain . Experiments were done to measure spinal levels of SOD2 protein and activity , inactivated SOD2 protein , and ROS accumulating dorsal horn cells after capsaicin injection to mouse foot with or without ROS scavengers . The capsaicin -induced hyperalgesia was determined in mice after manipulating SOD levels . Results showed that following capsaicin treatment , spinal levels of SOD2 activity were decreased , inactivated SOD2 proteins were increased , but total SOD2 proteins were unchanged . These changes were reversed with ROS scavengers . Mice showed enhanced or reduced hyperalgesia with decreased or increased SOD2 levels , respectively . The number of ROS accumulating cells was increased in SOD2KO mice but decreased in SOD2Tg mice . The data suggest that SOD2 activity levels determine the ROS accumulation , which in turn determines the levels of central sensitization and capsaicin -induced secondary hyperalgesia . Therefore , this study suggests a therapeutic potential of targeting SOD2 in persistent pain conditions . |