title: Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats.
abstract: Spinal cord injury (SCI) can cause neuropathic pain (NeP), often reducing a patient's quality of life. We recently reported that granulocyte colony-stimulating factor (G-CSF) could attenuate NeP in several SCI patients. However, the mechanism of action underlying G-CSF-mediated attenuation of SCI-NeP remains to be elucidated. The purpose of the present study was to elucidate the therapeutic effect and mechanism of action of granulocyte colony-stimulating factor for SCI-induced NeP. T9 level contusive SCI was introduced to adult male Sprague Dawley rats. Three weeks after injury, rats received intraperitoneal recombinant human G-CSF (15.0 μg/kg) for 5 days. Mechanical allodynia was assessed using von Frey filaments. Immunohistochemistry and western blot analysis were performed in spinal cord lumbar enlargement samples. Testing with von Frey filaments showed significant increase in the paw withdrawal threshold in the G-CSF group compared with the vehicle group 4 weeks, 5 weeks, 6 weeks and 7 weeks after injury. Immunohistochemistry for CD11b (clone OX-42) revealed that the number of OX-42-positive activated microglia was significantly smaller in the G-CSF group than that in the vehicle rats. Western blot analysis indicated that phosphorylated-p38 mitogen-activated protein kinase (p38MAPK) and interleukin-1β expression in spinal cord lumbar enlargement were attenuated in the G-CSF-treated rats compared with that in the vehicle-treated rats. The present results demonstrate a therapeutic effect of G-CSF treatment for SCI-induced NeP, possibly through the inhibition of microglial activation and the suppression of p38MAPK phosphorylation and the upregulation of interleukin-1β.
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan. Electronic address: masaokod@gmail.com.
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sakuma
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Taigo
authors.initials: T
authors.lastname: Inada
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Kamiya
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maki
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, University of Tsukuba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Aramomi
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.affiliation: Department of Orthopedic Surgery, Chiba Aoba Municipal Hospital, Japan.
authors.forename: Chikato
authors.initials: C
authors.lastname: Mannoji
authors.affiliation: Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Furuya
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D016179:Granulocyte Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Allodynia; Central pain; G-CSF; Inflammatory cytokine; Neuropathic pain; Spinal cord injury