title: Intradermal Injection with Nerve Growth Factor: A Reproducible Model to Induce Experimental Allodynia and Hyperalgesia.
abstract: BACKGROUND
  Nerve growth factor (NGF) plays a pivotal role in survival, growth, and differentiation of the nervous system. Increased levels of NGF have been reported in human pain disorders. Experimental injection of NGF in humans is known to evoke long-lasting mechanical sensitization and subsequent allodynia and hyperalgesia.
  
  
  METHODS
  Reproducibility of intradermal injection of NGF was investigated. Twenty healthy male volunteers were included (mean age 24 years, range 19 to 31). The experiment consisted of 3 identical treatment periods with period 1 stimulating the right arm, period 2 the left arm, and period 3 stimulating the right arm again (period one and three were separated by at least 21 days). Pain intensity was assessed in response to several phasic stimuli in 3 adjacent sites of the volar forearm: pressure; pinprick; brush; and heat before and after NGF injection. Additionally, areas of allodynia and secondary hyperalgesia were assessed. Rekindling with pressure was performed 1 hour and 24 hours after injection. Reproducibility was assessed with intraclass correlation coefficient (ICC 3,1).
  
  
  RESULTS
  ICC values > 0.6 for all phasic stimuli and for the area of hyperalgesia. After NGF injection, pressure pain (P < 0.001) and heat pain (P < 0.01) sensitivity increased significantly. After rekindling, the area of hyperalgesia (von Frey 26 g) was significantly increased (P = 0.03) and sensitivity to pinprick was increased (P < 0.02).
  
  
  CONCLUSIONS
  Intradermal NGF injection is capable of inducing reproducible allodynia and hyperalgesia, and the model is recommended for future experimental and pharmacological pain studies.
authors.affiliation: Department of Gastroenterology & Hepatology, Center of Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Andresen
authors.affiliation: Department of Gastroenterology & Hepatology, Center of Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Matias
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Department of Gastroenterology & Hepatology, Center of Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Anders Klitgaard
authors.initials: AK
authors.lastname: Nielsen
authors.affiliation: Department of Gastroenterology & Hepatology, Center of Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Lassen
authors.affiliation: Department of Health Science and Technology, Center for Sensory-Motor Interactions (SMI), Aalborg University, Aalborg, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: Department of Gastroenterology & Hepatology, Center of Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.|Department of Health Science and Technology, Center for Sensory-Motor Interactions (SMI), Aalborg University, Aalborg, Denmark.
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D001132:Arm; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced*; D007271:Injections, Intradermal; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage; D010147:Pain Measurement; D010812:Physical Stimulation; D011312:Pressure; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: experimental pain model; hyperalgesia; nerve growth factor; pain; pain measurement