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, 131 (4), 413-7

Reactive Oxygen Species and Lipid Peroxidation Inhibitors Reduce Mechanical Sensitivity in a Chronic Neuropathic Pain Model of Spinal Cord Injury in Rats

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Reactive Oxygen Species and Lipid Peroxidation Inhibitors Reduce Mechanical Sensitivity in a Chronic Neuropathic Pain Model of Spinal Cord Injury in Rats

Shayne N Hassler et al. J Neurochem.

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.

Keywords: chronic neuropathic pain; mechanical sensitivity; oxidative stress; spinal cord injury.

Figures

Figure 1
Figure 1
Forelimb paw withdraw thresholds (PWT) after intrathecal injection of reactive oxygen species (ROS) and lipid peroxidation (LP) inhibitors. All baseline mean values are similar to each other with no significant difference from between groups. All pre-injection mean values are significantly different to the baseline mean values. 0.1mg/kg Apocynin and 1.0mg/kg 4-oxo-tempo show the best recovery of mechanical sensitivity with near baseline measurements 30 and 60 minutes after injection. 0.1mg/kg Tirilizad also showed a significant effect, however this did not occur until 60 minutes after injection. Data are plotted as mean ± SEM. *p<0.05 compared to baseline mean values.
Figure 2
Figure 2
Hindlimb paw withdraw thresholds (PWT) after intrathecal injections of reactive oxygen species (ROS) and lipid peroxidation (LP) inhibitors. All baseline mean values are similar to each other with no significant difference from between groups. All pre-injection mean values are significantly different to the baseline mean values. 0.1mg/kg Apocynin and 1.0mg/kg 4-oxo-tempo show the best recovery of mechanical sensitivity, with both being significantly different at 30, 60, and 120 minutes after injection. 0.1mg/kg Tirilizad is also significantly different 30 and 120 minutes after injection. 1.0mg/kg U-83836E was significantly different 120 minutes after injection. Data are plotted as mean ± SEM. *p<0.05 compared to baseline mean values.

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