Korean J Pain.  2010 Sep;23(3):179-185. 10.3344/kjp.2010.23.3.179.

Antinociceptive Effect of Memantine and Morphine on Vincristine-induced Peripheral Neuropathy in Rats

• Park BY
• Park SH
• Kim WM
• Yoon MH
• Lee HG

• KMID: 1767875
• DOI: http://doi.org/10.3344/kjp.2010.23.3.179

Abstract

BACKGROUND
Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats.
METHODS
Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated.
RESULTS
Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle.
CONCLUSIONS
Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Keyword

antinociception; memantine; morphine; neuropathic pain; vincristine

MeSH Terms

Animals
Humans
Hyperalgesia
Injections, Intraperitoneal
Male
Memantine
Morphine
Neuralgia
Peripheral Nervous System Diseases
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Vincristine
Memantine
Morphine
Receptors, N-Methyl-D-Aspartate
Vincristine

Figure

• 

  Fig. 1 Time course of hind paw withdrawal response to von Frey filaments after vincristine treatment. Data are presented as withdrawal threshold. Each line represents mean ± SEM of 8 rats. BL: baseline withdrawal threshold measured before vincristine treatment. Significant differences between saline (control) and vincristine treatment are indicated. *P < 0.05, †P < 0.01.

• 

  Fig. 2 Effects of intraperitoneal memantine for hindpaw withdrawal response to von Frey filaments after vincristine treatment. Data are presented as withdrawal threshold or percent of maximal possible effect (%MPE). Each line represents mean ± SEM of 6-7 rats. BL: baseline withdrawal threshold measured before vincristine treatment. Control data were measured immediately before intraperitoneal delivery of drug. Compared with vehicle (saline). *P < 0.01.

• 

  Fig. 3 Effects of intraperitoneal morphine for hindpaw withdrawal response to von Frey filaments after vincristine treatment. Data are presented as withdrawal threshold or percent of maximal possible effect (%MPE). Each line represents mean ± SEM of 6-7 rats. BL: baseline withdrawal threshold measured before vincristine treatment. Control data were measured immediately before intraperitoneal delivery of drug. Intraperitoneal morphine produced a dose-dependent increase in withdrawal threshold. Compared with vehicle (saline). *P < 0.05, †P < 0.01.

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