Dapsone Prevents Allodynia and Hyperalgesia and Decreased Oxidative Stress After Spinal Cord Injury in Rats

Abstract

Study Design. Prospective longitudinal experimental study. Objective. We evaluate the effect of dapsone on tactile allodynia and mechanical hyperalgesia and to determine its antioxidant effect in a spinal cord injury (SC) model in rats. Summary of Background Data. Neuropathic pain (NP) as result of traumatic spinal cord injury is a deleterious medical condition with temporal or permanent time-course. Painful stimuli trigger a cascade of events that activate the N-methyl-Daspartate (NMDA) receptor, inducing an increase in oxidative stress. Since there is no effective treatment for this condition, dapsone (4,4 0 diaminodiphenylsulfone) is proposed as potential treatment for NP. Its anti-oxidant, neuroprotective, and antiinflammatory properties have been documented, however, there is no evidence regarding its use for treatment of NP induced by SCI. Methods. In this study, we evaluated the anti-allodynic and anti-hyperalgesic effect of dapsone as preventive or acute treatment after NP was already established. Furthermore, partici-pation of oxidative stress was evaluated by measuring lipid peroxidation (LP) and glutathione concentration (GSH) in rats with SCI. Results. Acute treatment with dapsone (3.1-25 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH in the injured tissue 15 days after the injury was produced. On the other hand, preventive treatment (3 h post-injury, once daily for 3 days) with dapsone (3.1-25 mg/kg, i.p.) yielded similar results. Conclusion. The findings suggest that the anti-nociceptive effect of dapsone is regulated through the decrease of oxidative stress and the excitotoxicity is associated with the activation of NMDA receptors.

Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms

“…Dapsone has demonstrated the ability to attenuate the development of striatal necrosis [ 148 ] and the depletion of gamma-aminobutyric acid levels [ 149 ] after the injection of quinolinic acid, a neurotoxic NMDA receptor agonist. Dapsone might prevent excessive lipid peroxidation [ 148 ] or glutamate agonism [ 149 ], which was corroborated by a spinal cord injury (SCI) murine model in which dapsone appeared to antagonize lipid peroxidase and normalize glutathione concentrations [ 150 ]. Notably, tactile allodynia and mechanical hyperalgesia were similarly improved with either early (3 hours post-injury) or delayed administration (15 days post-injury) of dapsone [ 150 ].…”

“…Dapsone might prevent excessive lipid peroxidation [ 148 ] or glutamate agonism [ 149 ], which was corroborated by a spinal cord injury (SCI) murine model in which dapsone appeared to antagonize lipid peroxidase and normalize glutathione concentrations [ 150 ]. Notably, tactile allodynia and mechanical hyperalgesia were similarly improved with either early (3 hours post-injury) or delayed administration (15 days post-injury) of dapsone [ 150 ]. Other SCI murine models have shown that dapsone can improve neurological function by reducing cell apoptosis [ 151 ] and inhibiting myeloperoxidase [ 152 ], limiting the extent of neurological tissue damage.…”