title: Thermal hyperalgesia assessment for rats after spinal cord injury: developing a valid and useful pain index.
abstract: BACKGROUND
  Ongoing research to understand the mechanism behind pain is heavily dependent on animal testing. However, unlike humans, animal subjects cannot directly communicate with researchers to express the degree of pain they are experiencing. Therefore, measuring the presence of pain in animal studies is based on behavioral tests. The use of arbitrary values for determining the presence of pain in animal studies is an oversimplification of a complex and cortically dependent process.
  
  
  OBJECTIVE
  The purpose of the present study was to identify a statistically supported latency time indicator that can be used as an accurate index for hyperalgesia to thermal stimuli in Sprague-Dawley rats subjected to T9 contusive spinal cord injury (SCI).
  
  
  METHODS
  A statistical analysis of latency of withdrawal from stimulus-mediated spinal reflex in 979 Sprague-Dawley rats that had been subjected to a T9 contusive SCI was performed.
  
  
  METHODS
  This is a retrospective review of a large research database derived from a series of studies performed evaluating thermal hyperalgesia in rats after SCI. Sprague-Dawley rats underwent a T9 contusive SCI and were tested for withdrawal latency from a heat stimulus. Assessment was done preinjury and on Postinjury Days 21, 28, 35, and 42 of the chronic phase of injury via a plantar withdrawal test.
  
  
  RESULTS
  The baseline test results of the 979 rats showed a significant resemblance to the normal distribution. The observed change in withdrawal showed mean latency drops of 0.42 second (standard error of the mean [SEM], 0.18; p=.026), 0.57 second (SEM, 0.19; p=.004), 0.63 second (SEM, 0.19; p=.002), and 0.69 second (SEM, 0.19; p=.0003). The standard deviation from the mean at all four postsurgical assessments was between 2.8 and 2.9 seconds.
  
  
  CONCLUSIONS
  Interpretation of withdrawal latency times as a marker for thermal hyperalgesia must be based on an appreciation for the normal distribution of pain scores. Recognizing that withdrawal latency is normally distributed both before and after injury allows for rational assignment of animals to groups designated as hyperalgesic and nonhyperalgesic. Two point nine seconds faster than the mean latency time is a statistically reliable indicator of thermal hyperalgesia in Sprague-Dawley rats subjected to contusive SCI. Repeated testing of animals to establish the presence or absence of thermal hyperalgesia beyond 21 days is not necessary in the absence of intervention.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Hung Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Taehee
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Novotny
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Nayab
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: James
authors.initials: J
authors.lastname: Aksamit
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Siegel
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA.
authors.forename: Gurwattan S
authors.initials: GS
authors.lastname: Miranpuri
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, K4/882, Clinical Science Center, 600 Highland Ave, Madison, WI 53792, USA. Electronic address: resnick@neurosurgery.wisc.edu.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Resnick
mesh_terms: D000818:Animals; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors
keywords: Neuropathic pain; Plantar test; Spinal cord injury; Spinal reflex; Statistical analysis; Thermal hyperalgesia; Withdrawal latency time