Korean J Pain.  2015 Jul;28(3):185-192. 10.3344/kjp.2015.28.3.185.

Olanzapine Attenuates Mechanical Allodynia in a Rat Model of Partial Sciatic Nerve Ligation

• Fukuda T
• Yamashita
• Hisano S
• Tanaka M

• KMID: 2149462
• DOI: http://doi.org/10.3344/kjp.2015.28.3.185

Abstract

BACKGROUND
Neuropathic pain is a global clinical problem; nevertheless, nerve injury treatment methods remain limited. Olanzapine has antinociceptive and anti-nueropathic properties; however, its preventive effects have not been assessed in nerve injury models.
METHODS
We prepared a partial sciatic nerve ligation (Seltzer model) or sham-operated model in male Sprague-Dawley rats under isoflurane anesthesia. In a pre-treatment study, we administered olanzapine (10 mg/kg) intraperitoneally 1 h before nerve ligation. In post-treatment and dose-dependent studies, we injected 3 different doses of olanzapine intraperitoneally 1 h after nerve ligation. Mechanical allodynia was measured before and 7 days after surgery. Immunohistochemical analysis using anti-Iba-1 antibody was used to assess the effect of olanzapine at the spinal level.
RESULTS
In the pre-treatment study, median withdrawal thresholds of the normal saline groups were significantly lower than those of the sham-operated groups; however, those of the olanzapine (10 mg/kg) and sham-operated groups were not different. In the post-treatment and dose-dependent studies, the median withdrawal thresholds of the olanzapine (2.5 mg/kg) and normal saline groups were not different; however, those of the olanzapine (10 and 50 mg/kg) groups were significantly higher than those of the normal saline groups. Olanzapine did not have a significant effect on the density of Iba-1 staining.
CONCLUSIONS
Olanzapine attenuated mechanical allodynia dose-dependently in the Seltzer model. This anti-allodynic effect of olanzapine was observed even when injected 1 h after nerve ligation. This effect of olanzapine appeared to be unrelated to microglia activation in the ipsilateral dorsal horn of the lumbar spinal cord.

Keyword

Mechanical allodynia; Microglia; Neuropathic pain; Olanzapine; Rat model; Spinal dorsal horn

MeSH Terms

Anesthesia
Animals
Horns
Humans
Hyperalgesia*
Isoflurane
Ligation*
Male
Microglia
Models, Animal*
Neuralgia
Rats, Sprague-Dawley
Sciatic Nerve*
Spinal Cord
Isoflurane

Figure

• 

  Fig. 1 Mechanical withdrawal threshold of pre-treatment groups on the 7th day after partial sciatic nerve ligation (pSNL). Sham, NS, and Olanzapine indicate sham-operation + vehicle (normal saline), pSNL-operation + vehicle (normal saline), and pSNL-operation + olanzapine (10 mg/kg) groups, respectively. Median thresholds are indicated with horizontal bars. The vertical bars indicate the range and horizontal boundaries of the boxes represent the first and third quartiles. *P < 0.05 vs. Sham-operation group.

• 

  Fig. 2 Mechanical withdrawal threshold of post-treatment groups on the 7th day after partial sciatic nerve ligation (pSNL). Sham, NS, and Olanzapine indicate sham-operation + vehicle (normal saline), pSNL-operation + vehicle (normal saline), and pSNL-operation + olanzapine (10 mg/kg) groups, respectively. Median thresholds are indicated with horizontal bars. The vertical bars indicate the range and horizontal boundaries of the boxes represent the first and third quartiles. *P < 0.05 vs. Sham-operation group.

• 

  Fig. 3 Dose-dependency of mechanical withdrawal threshold in the post-treatment groups at the 7th day after partial sciatic nerve ligation (pSNL). *P < 0.05 vs. pSNL-operation + vehicle (normal saline) group.

• 

  Fig. 4 Typical Iba-1 staining of the pre- and post-treatment groups in the ipsilateral dorsal horn of the lumbar spinal cord (L5). Sham, NS, and Olanza indicate sham-operation + vehicle (normal saline), partial sciatic nerve ligation (pSNL) + vehicle, and pSNL + olanzapine (10 mg/kg) groups, respectively. Scale bar = 100 µm.

• 

  Fig. 5 Percentage of Iba-1-immunoreactive area of the pre- and post-treatment groups in the ipsilateral dorsal horn of the lumbar spinal cord (L5). Sham, NS, and Olanzapine indicate sham-operation + vehicle (normal saline), partial sciatic nerve ligation (pSNL) + vehicle (normal saline), and pSNL + olanzapine (10 mg/kg) groups, respectively. *P < 0.05 vs. Sham-operation + vehicle (normal saline) group.

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