title: Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model.
abstract: BACKGROUND
  The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model.
  
  
  METHODS
  The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored.
  
  
  RESULTS
  Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice.
  
  
  CONCLUSIONS
  The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.
authors.affiliation: School of Medicine, Chiba University Chiba, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Orthopedic Surgery, Kitasato University Kanagawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: School of Medicine, Chiba University Chiba, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kamoda
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oikawa
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kubota
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inage
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sainoh
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedic Surgery, East Chiba Medical Center Chiba, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Orthopedic Surgery, Teikyo University Mizonokuchi Hospital Kawasaki, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Toyone
authors.affiliation: Department of Orthopedic Surgery, Kitasato University Kanagawa, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Bioenvironmental Medicine, Graduate school of Medicine, Chiba University Chiba, Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University Chiba, Japan.
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000378:metabolism*; D019807:Iodoacetic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D015740:Calcitonin Gene-Related Peptide; D019807:Iodoacetic Acid
keywords: Osteoarthritis; mice model; monoiodoacetate (MIA); tumor necrosis factor (TNF)-alpha