title: Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve.
abstract: METHODS
  Animal experimental study with intervention.
  
  
  OBJECTIVE
  The aim of this study was to elucidate therapeutic effects of delayed granulocyte colony-stimulating factor treatment for mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats.
  
  
  BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF) is used clinically for patients with hematological disorders. Previous reports showed that immediate G-CSF attenuates neuropathic pain in CCI of the sciatic nerve. However, the acute treatment for neuropathic pain prior to accurate diagnosis is not realistic in clinical settings.
  
  
  METHODS
  Adult, female Sprague-Dawley rats were subjected to the CCI model. This model induces mechanical allodynia on the ipsilateral hind paw within the first week after the injury. One week after CCI, rats received intraperitoneal G-CSF (15.0 μg/kg) for 5 consecutive days. Mechanical allodynia was assessed using the von Frey hair test. Immunohistochemistry for phosphorylated p38 mitogen-activated kinase (p-p38MAPK) and OX-42 (a marker for activated microglia) on tissue slides from a subset of rats 2 weeks after surgery. Western blot analyses were carried out to determine protein expression level of p-p38MAPK and interleukin-1 β on spinal cord homogenates 2 weeks after CCI.
  
  
  RESULTS
  Results of the von Frey filament test showed that G-CSF significantly attenuates mechanical allodynia induced by the CCI model. Immunohistochemistry revealed that G-CSF reduced the number of p-p38MAPK-positive cells in the ipsilateral dorsal horn compared with that in the vehicle group rats. Immunofluorescent double staining revealed that p-p38MAPK-expressing cells in the spinal cord dorsal horn are mainly microglia. Western blot analysis indicated that G-CSF decreased the expression levels of both p-p38MAPK and interleukin-1 β in the ipsilateral dorsal horn compared with that in the vehicle group rats.
  
  
  CONCLUSIONS
  The present results indicate a beneficial effect of delayed G-CSF treatment in an animal model of peripheral nerve injury-induced neuropathic pain.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopedic Surgery, Chiba Medical Center, Chiba, Japan †Graduate School of Medicine, Chiba University, Chiba Medical Center, Chiba, Japan ‡Chiba Aoba Municipal Hospital, Chiba Medical Center, Chiba, Japan; and §Department of Orthopedic Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Takeo
authors.initials: T
authors.lastname: Furuya
authors.forename: Kei
authors.initials: K
authors.lastname: Kato
authors.forename: Chikato
authors.initials: C
authors.lastname: Mannoji
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Taigo
authors.initials: T
authors.lastname: Inada
authors.forename: Koshiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Ota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor