title: Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.
abstract: Chronic neuropathic pain is a common consequence of spinal cord injury (SCI), develops over time and negatively impacts quality of life, often leading to substance abuse and suicide. Recent evidence has demonstrated that reactive oxygen species (ROS) play a role in contributing to neuropathic pain in SCI animal models. This investigation examines four compounds that reduce ROS and the downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and tirilazad, and tests if these compounds can reduce nocioceptive behaviors in chronic SCI animals. Apocynin and 4-oxo-tempo significantly reduced abnormal mechanical hypersensitivity measured in forelimbs and hindlimbs in a model of chronic SCI-induced neuropathic pain. Thus, compounds that inhibit ROS or lipid peroxidation products can be used to ameliorate chronic neuropathic pain. We propose that the application of compounds that inhibit reactive oxygen species (ROS) and related downstream molecules will also reduce the behavioral measures of chronic neuropathic pain. Injury or trauma to nervous tissue leads to increased concentrations of ROS in the surviving tissue. Further damage from ROS molecules to dorsal lamina neurons leads to membrane excitability, the physiological correlate of chronic pain. Chronic pain is difficult to treat with current analgesics and this research will provide a novel therapy for this disease.
authors: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.
authors: Shayne N
authors: SN
authors: Hassler
authors: Kathia M
authors: KM
authors: Johnson
authors: Claire E
authors: CE
authors: Hulsebosch
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000150:complications* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D013119:Spinal Cord Injuries / Q000150:complications
chemical_list: D000098:Acetophenones; D005227:Fatty Acids; D017382:Reactive Oxygen Species; C013584:lipid peroxidation inhibitor; C056165:acetovanillone
keywords: chronic neuropathic pain; mechanical sensitivity; oxidative stress; spinal cord injury