Hung Tae Kim1, Taehee Kim1, Brianna Novotny1, Nayab Khan1, James Aksamit1, Steven Siegel1, Gurwattan S Miranpuri1, Daniel K Resnick2. 1. 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. 2. 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.
Abstract
BACKGROUND CONTEXT: 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. PURPOSE: 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). STUDY DESIGN: 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.
BACKGROUND CONTEXT: 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. PURPOSE: 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). STUDY DESIGN: 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: Marissa Zubia McMackin; Matthew R Lewin; Dennis R Tabuena; F Eric Arreola; Christopher Moffatt; Megumi Fuse Journal: J Neurosci Methods Date: 2015-10-09 Impact factor: 2.390
Authors: Gurwattan S Miranpuri; Dominic T Schomberg; Bahauddeen Alrfaei; Kevin C King; Bryan Rynearson; Vishwas S Wesley; Nayab Khan; Kristen Obiakor; Umadevi V Wesley; Daniel K Resnick Journal: Ann Neurosci Date: 2016-03-11
Authors: Mostafa M Ahmed; HyunKyung Lee; Zach Clark; Gurwattan S Miranpuri; Carrie Nacht; Kush Patel; Lisa Liu; Jiliian Joslin; Douglus Kintner; Daniel K Resnick Journal: Ann Neurosci Date: 2014-07
Authors: Gurwattan S Miranpuri; Justyn Nguyen; Neydis Moreno; Noemi A Yutuc; Jason Kim; Seah Buttar; Greta R Brown; Sydney E Sauer; Chandra K Singh; Saurabh Kumar; Daniel K Resnick Journal: Ann Neurosci Date: 2019-04-01