title: A fracture pain model in the rat: adaptation of a closed femur fracture model to study skeletal pain.
abstract: BACKGROUND
  Because of the relative lack of understanding of the mechanisms that drive skeletal pain, the purpose of this study was to adapt a previously validated closed femur fracture model to quantitatively evaluate skeletal pain in female and male rats.
  
  
  METHODS
  Three-month-old female and male Sprague-Dawley rats were anesthetized, and a stainless steel pin was inserted into the intramedullary space of the left femur. Three weeks later, the rats were reanesthetized, and left femoral diaphyses were fractured using a standardized impactor device. At 1-21 days after fracture, skeletal pain was measured by quantitatively assessing spontaneous guarding, spontaneous flinching, and weight bearing of the fractured hind limb.
  
  
  RESULTS
  Females and males showed highly robust pain behaviors that were maximal at day 1 after fracture and returned gradually to normal nonfractured levels at days 14-21 after fracture. The magnitude of fracture pain was not significantly different at most time points between female and male rats. In both females and males, the pain-related behaviors were attenuated by subcutaneous morphine in a dose-dependent manner.
  
  
  CONCLUSIONS
  This model may help in developing a mechanism-based understanding of the factors that generate and maintain fracture pain in both females and males and in translating these findings into new therapies for treating fracture pain.
authors.affiliation: Neurosystems Center and Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Katie T
authors.initials: KT
authors.lastname: Freeman
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Koewler
authors.forename: Juan M
authors.initials: JM
authors.lastname: Jimenez-Andrade
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Buus
authors.forename: Monica B
authors.initials: MB
authors.lastname: Herrera
authors.forename: Carl D
authors.initials: CD
authors.lastname: Martin
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ghilardi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuskowski
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Mantyh
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009020:Morphine