Reactive Oxygen Species and Lipid Peroxidation Products Contribute to Neuropathic Pain in Chronic Spinal Cord Injured Rats

Spinal cord injury (SCI) can result in loss of locomotion, sexual and bladder function, and chronic neuropathic pain. A rat model of spinal cord injury was used to study the mechanisms of chronic neuropathic pain. Chronically up-regulated reactive oxygen species (ROS) generated in neurons as a result of spinal cord injury contribute to the chronic neuropathic pain measured in rats. When ROS was reduced in chronic SCI by using PBN, a ROS scavenger, there was a reduction in neuropathic pain behaviors and a reduction in hyperexcitability of dorsal horn neurons in rats. Compounds that reduce ROS and lipid peroxidation are able to reduce measures of chronic neuropathic pain. Mechanical allodynia was reduced in chronic SCI rats with the intrathecal administration of Apocynin, 4-OXO-TEMPO, Tirilazad, and U-83836E. Apocynin was used to further examine the ability of ROS and lipid peroxidation products to generate neuropathic pain behaviors in chronic SCI rats. Apocynin was found to reduce expression of 4-HNE, a lipid peroxidation product, in chronic SCI rats when administered intraperitoneally 30 minutes before perfusion and fixation. Evoked and non-evoked measures of neuropathic pain were reduced in chronic SCI rats when Apocynin was applied intrathecally and intraperitoneally. Apocynin was also able to reduce hyperexcitability of dorsal horn neurons in chronic SCI rats. These findings indicate that ROS is a major contributor to chronic neuropathic pain resulting from SCI. Further investigation of the relationship between reactive oxygen species and chronic neuropathic pain may lead to better understanding of the biological processes of chronic pain and more effective therapies for treating injury induced neuropathic pain.