Korean J Pain.  2015 Apr;28(2):96-104. 10.3344/kjp.2015.28.2.96.

Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in Combination in Rodent Neuropathic Pain Model

• Nasirinezhad F
• Hosseini M
• Salari S

• KMID: 2278266
• DOI: http://doi.org/10.3344/kjp.2015.28.2.96

Abstract

BACKGROUND
The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain.
METHODS
Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a 44degrees C water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system.
RESULTS
SHG at 0.5 and 1 microg significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 microg (P < 0.001) of SHG. 1 microg of noradrenaline, but not 0.5 microg, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy.
CONCLUSIONS
Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.

Keyword

Antagonists and Inhibitors; Neuropathic pain; Noradrenaline; N-Methyl-D-Aspartate; Receptors

MeSH Terms

Acetone
Analgesia
Baths
Constriction
Hand Strength
Hot Temperature
Hyperalgesia
Injections, Spinal
N-Methylaspartate*
Neuralgia*
Norepinephrine*
Reflex
Rodentia*
Sciatic Nerve
Serine
Subarachnoid Space
Water
Acetone
N-Methylaspartate
Norepinephrine
Serine
Water

Figure

• 

  Fig. 1 Percentage of withdrawal response to the acetone drops in the drug-treated CCI groups, vehicle-treated CCI group, and control animals (A, B). The comparison between the theoretical effectiveness and the effectiveness of the experimental combination therapy is shown in (C). The combination therapy decreased the effectiveness of the treatment. The results are expressed as the mean ± SEM of the 8 animals in each group. *P < 0.05, **P < 0.01, ***P < 0.001; NA: noradrenaline, SHG: serine histogranin.

• 

  Fig. 2 Withdrawal latencies in response to the 44℃ water in the drug-treated CCI groups, vehicle-treated CCI group, and control animals (A, B). The comparison between the theoretical effectiveness and the effectiveness of the experimental combination therapy is shown in (C). The effectiveness was significantly reduced in the case of combination therapy with equal doses. The results are expressed as the mean ± SEM of the 8 animals in each group. *P < 0.05, **P < 0.01; NA: noradrenaline, SHG: serine histogranin.

• 

  Fig. 3 Changes in the number of positive grasping (A, B) and placing reflexes (C, D) after intrathecal injection of noradrenaline (NA) or serine histogranin (SHG), alone or in combination, in the different experimental groups. The drug therapy did not improve the motor reflexes. The results are expressed as the mean ± SEM of the 8 animals in each group.

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