title: Effect of administration of antibodies against nerve growth factor in a rat model of muscle injury.
abstract: BACKGROUND
  Although muscle injury is a common source of pain, the mechanism causing such pain is not completely known. We have previously reported nerve growth factor (NGF) as a proinflammatory mediator involved in acute pain, and clinical trials have shown the effectiveness of anti-NGF antibodies for management of low back pain. Here, we aim to examine the effects of anti-NGF antibodies on muscle-derived pain by studying their effects on sensory innervation in a rat muscle injury model.
  
  
  METHODS
  A nervous system tracer, Fluoro-Gold, was applied to both gastrocnemius muscles of 24 male Sprague Dawley rats to stain the sensory nerves. Then, the drop-mass method was used to damage the right gastrocnemius muscle of the posterior limb. Anti-NGF antibodies (50μL) were injected into the injured muscles in 12 rats. Tissues were evaluated 1, 3, and 7 days post-injury by performing haematoxylin-and-eosin (HE) staining. The percentage of the total number of FG-positive cells that were also positive for a pain-related neuropeptide, calcitonin gene-related peptide (CGRP), was determined for the bilateral dorsal root ganglia from L1 to L6 7 days post-injury.
  
  
  RESULTS
  HE staining showed active inflammation, indicated by increased basophil and eosinophil accumulation, at the injury site 1 and 3 days post-injury, as well as scar tissue formation 7 days post-injury. Injection of anti-NGF reduced muscle necrosis 1 and 3 days post-injury, and resulted in replacement of granulation tissue and muscle fibre regeneration 7 days post-injury. Anti-NGF also significantly inhibited CGRP among FG-positive cells (treatment group 38.2%, control group 49.6%; P<0.05).
  
  
  CONCLUSIONS
  This study found active inflammation induced by NGF, which may contribute to pain after muscle injury. Anti-NGF antibodies successfully suppressed the pain mediator NGF and inhibited inflammation, suggesting NGF as a target for control in pain management.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan. Electronic address: kazuhideinage@yahoo.co.jp.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inage
authors.affiliation: Department of Orthopaedic Surgery, National Hospital Organization, Chiba Medical Center, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Bioenvironmental Medicine Graduate School of Medicine Chiba University, Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Bioenvironmental Medicine Graduate School of Medicine Chiba University, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kubota
authors.affiliation: Department of Orthopaedic Surgery, Chiba Children's Hospital, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oikawa
authors.affiliation: Dept of Orthopaedic Surgery, Sainou Hospital, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sainoh
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shiga
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kanamoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D010146:Pain / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000906:Antibodies; D005456:Fluorescent Dyes; D013266:Stilbamidines; D020932:Nerve Growth Factor
keywords: Acute-phase response; Antibodies nerve growth factor; Calcitonin gene-related peptide; Dorsal root ganglia; Gastrocnemius muscle; Haematoxylin-and-eosin (HE) staining; Muscle injury; Pain; Proinflammatory cytokines; Tissue repair