The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerolinduced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 μg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 μg per rat; selective 5-HT 1A receptor antagonist), SB-224289 (5 μg per rat; selective 5-HT 1B receptor antagonist), BRL-15572 (4 μg per rat; selective 5-HT 1D receptor antagonist), and SB-659551 (6 μg per rat; selective 5-HT 5A receptor antagonist), but naloxone (50 μg per rat; nonselective opioid receptor antagonist) did not prevent the [6]-gingerol-induced antiallodynic effect. Moreover, intrathecal administration of Nω-nitro-L-arginine methyl ester (100 μg per rat; nonselective nitric oxide [NO] synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μg per rat; inhibitor of guanylate cyclase), and glibenclamide (50 μg per rat; channel blocker of adenosine triphosphate [ATP]-sensitive K + channels) prevented the [6]-gingerol-induced antiallodynic effect. These data suggest that the antiallodynic effect induced by [6]-gingerol is mediated by the serotoninergic system involving the activation of 5-HT 1A/1B/1D/5A receptors, as well as the NO-cyclic guanosine monophosphate-ATP-sensitive K + channel pathway but not by the opioidergic system.

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Background: Dapsone (4,4'-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death. Objective: To provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials. Methods: We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death. Conclusion: The evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

Background: Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI. Methods: To produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25-50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue. Results: Acute treatment with amantadine reduced nociceptive behaviour.Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine. Conclusions: Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N-methyl-D-aspartate receptors activation. Significance: This study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dosedependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain.However, further research is required to provide evidence of the effectiveness and feasibility.How to cite this article: Mata-Bermudez A, Ríos C, Burelo M, et al. Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats.

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.