title: Objective validation of central sensitization in the rat UVB and heat rekindling model.
abstract: BACKGROUND
  The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model.
  
  
  METHODS
  The UVB/HR model was induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h after UVB irradiation. MWT was compared between UVB/HR and SHAM-treated rats (anaesthetic only). Underlying central mechanisms in the model were pharmacologically validated by MWT measurement following intrathecal N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, or saline.
  
  
  RESULTS
  Secondary hyperalgesia was confirmed by a significantly lower pre-drug MWT {mean [±standard error of the mean (SEM)]} in UVB/HR [56.3 (±2.1) g/mm(2) , n = 15] compared with SHAM-treated rats [69.3 (±2.9) g/mm(2) , n = 8], confirming face validity of the model. Predictive validity was demonstrated by the attenuation of secondary hyperalgesia by MK-801, where mean (±SEM) MWT was significantly higher [77.2 (±5.9) g/mm(2) n = 7] in comparison with pre-drug [57.8 (±3.5) g/mm(2) n = 7] and saline [57.0 (±3.2) g/mm(2) n = 8] at peak drug effect. The occurrence of central sensitization confirmed construct validity of the UVB/HR model.
  
  
  CONCLUSIONS
  This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain.
authors.affiliation: School of Physiology and Pharmacology, University of Bristol, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Weerasinghe
authors.forename: B M
authors.initials: BM
authors.lastname: Lumb
authors.forename: R
authors.initials: R
authors.lastname: Apps
authors.forename: S
authors.initials: S
authors.lastname: Koutsikou
authors.forename: J C
authors.initials: JC
authors.lastname: Murrell
mesh_terms: D000818:Animals; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014466:Ultraviolet Rays
chemical_list: D016291:Dizocilpine Maleate