Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats.

Abstract

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 dose-dependent 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.

• Authors: Alfonso Mata-Bermudez, Camilo Ríos, Masha Burelo, Cuauhtémoc Pérez-González, Betzabé Anahí García-Martínez, Gustavo Jardon-Guadarrama, Francisco Calderón-Estrella, Norman Manning-Balpuesta, Araceli Diaz-Ruiz
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 25 Issue 8 Pg. 1839-1851 (09 2021) ISSN: 1532-2149 [Electronic] England
• PMID: 33982314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 European Pain Federation - EFIC®.

Chemical References

• Pharmaceutical Preparations
• Receptors, N-Methyl-D-Aspartate
• Amantadine

Topics

• Amantadine (pharmacology, therapeutic use)
• Animals
• Female
• Neuralgia
• Oxidative Stress
• Pharmaceutical Preparations
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Spinal Cord (metabolism)
• Spinal Cord Injuries (complications, drug therapy)