Korean J Pain.  2010 Sep;23(3):172-178. 10.3344/kjp.2010.23.3.172.

Antiallodynic Effect of Thalidomide and Morphine on Rat Spinal Nerve Ligation-induced Neuropathic Pain

• Choi JI
• Kim WM
• Yoon MH
• Lee HG

• KMID: 1767873
• DOI: http://doi.org/10.3344/kjp.2010.23.3.172

Abstract

BACKGROUND
Tumor necrosis factor-alpha and other proinflammatory cytokines are becoming well recognized as key mediators in the pathogenesis of many types of neuropathic pain. Thalidomide has profound immunomodulatory actions in addition to their originally intended pharmacological actions. There has been debate on the analgesic efficacy of opioids in neuropathic pain. The aim of this study was to investigate the effect of thalidomide and morphine on a spinal nerve ligation model in rats.
METHODS
Male Sprague-Dawley rats weighing 100-120 g were used. Lumbar (L) 5 and 6 spinal nerve ligations were performed to induce neuropathic pain. For assessment of mechanical allodynia, mechanical stimulus using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of intraperitoneal thalidomide (6.25, 12.5, 25 and 50 mg/kg, respectively) and morphine (3 and 10 mg/kg, respectively) were examined on a withdrawal threshold evoked by spinal nerve ligation.
RESULTS
After L5 and 6 spinal nerve ligation, paw withdrawal thresholds on the ipsilateral side were significantly decreased compared with pre-operative baseline and with those in the sham-operated group. Intraperitoneal thalidomide and morphine significantly increased the paw withdrawal threshold compared to controls and produced dose-responsiveness.
CONCLUSIONS
Systemic thalidomide and morphine have antiallodynic effect on neuropathic pain induced by spinal nerve ligation in rat. These results suggest that morphine and thalidomide may be alternative therapeutic approaches for neuropathic pain.

Keyword

antinociceptive; cytokine; morphine; neuropathy; thalidomide

MeSH Terms

Analgesics, Opioid
Animals
Cytokines
Humans
Hyperalgesia
Ligation
Male
Morphine
Neuralgia
Rats
Rats, Sprague-Dawley
Spinal Nerves
Thalidomide
Tumor Necrosis Factor-alpha
Analgesics, Opioid
Cytokines
Morphine
Thalidomide
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Time course of the hindpaw-withdrawal response to von Frey filament stimulation after spinal nerve ligation. Data are presented as withdrawal threshold (g). Each line represents mean ± SEM of 8 rats. BL: baseline withdrawal threshold measured before spinal nerve ligation. Significant differences between the spinal nerve-ligated and sham-ligated groups are indicated. *P < 0.05, †P < 0.01, ‡P < 0.001 vs. sham.

• 

  Fig. 2 Effects of intraperitoneal thalidomide on the hindpaw-withdrawal response to von Frey filament stimulation after spinal nerve ligation. Data are presented as withdrawal threshold (A) or percentage of maximal possible effect (%MPE, B). Each line or bar represents mean ± SEM of 5-7 rats. Control studies were performed using intraperitoneal DMSO. Thalidomide produced a dose-dependent increase in withdrawal threshold. *P < 0.05, †P < 0.01 vs. control.

• 

  Fig. 3 Effects of intraperitoneal morphine on the hindpaw-withdrawal response to von Frey filament stimulation after spinal nerve ligation. Data are presented as withdrawal threshold (A) or percentage of maximal possible effect (%MPE, B). Each line or bar represents mean ± SEM of 5-7 rats. Control studies were performed using intraperitoneal saline. Morphine produced a dose-dependent increase in withdrawal threshold. *P < 0.05, †P < 0.01 vs. control.

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