title: Olanzapine Attenuates Mechanical Allodynia in a Rat Model of Partial Sciatic Nerve Ligation.
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.
authors.affiliation: Department of Anesthesiology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Anesthesiology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Laboratory of Neuroendocrinology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Setsuji
authors.initials: S
authors.lastname: Hisano
authors.affiliation: Department of Anesthesiology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
keywords: Mechanical allodynia; Microglia; Neuropathic pain; Olanzapine; Rat model; Spinal dorsal horn