Published: 2017-09-23

Change from baseline as an outcome illustrates escape behaviour of rats in hot plate method

Rama Mohan Pathapati, Manchi Rajesh Kumar, B. L. Kudagi, Madhavulu Buchineni


Background: The Hot Plate test is a thermal hyperalgesia model to assess the analgesic activity of many compounds. Traditional analysis compares reaction times with controls, reports only analgesic activity without considering escape reflex. Escape reflex to pain sensation also provides an indirect measure of analgesic activity. However, it requires repeated exposure of rats to hot plate. We explored the learning activities and escape behaviour of rats by calculating the change from baseline of reaction times.

Methods: Male Wister strain albino rats, weighing between 150-200mg were used for assessment of hot-plate induced hyperalgesia. Author analysed the analgesic activity of aspirin (100mg/Kg) and compared with animals receiving saline. Aspirin and saline were administered 1hr orally before the commencement of the experiment. The reaction time was recorded at every 30 min up to 6hrs.

Results: With traditional analysis, we can observe that the onset of action, peak action and duration of analgesic activity of aspirin was at 0.5, 2.0 and 5.0 hours respectively. Peak inhibition of reaction time was seen at 2 hours with a magnitude of 474%. When we applied a statistical procedure, absolute change from baseline statistics, we found that animals treated with aspirin also exhibited escape reflex after fading of drug response and animals treated with saline demonstrated early (0.5hr) escape behaviour from the hot plate and continued throughout the rest of the experiment.

Conclusions: Change from baseline as an outcome illustrates escape behaviour of rats in hot plate method and it should be employed along with percentage inhibition during assessment of analgesic activity.


Analgesic activity, Change from baseline, Escape reflex, Hot plate, Percentage inhibition

Full Text:



Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl-and dithienylbutylamines. Journal of Pharmacology and Experimental Therapeutics. 1953;107(3):385-93.

Matsumiya LC, Sorge RE, Sotocinal SG, Tabaka JM, Wieskopf JS, Zaloum A, et al. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. Journal of the american association for laboratory animal science. 2012;51(1):42-9.

Espejo EF, Mir D. Structure of the rat's behaviour in the hot plate test. Behavioural brain research. 1993;56(2):171-6.

LaBuda CJ, Fuchs PN. Low dose aspirin attenuates escape/avoidance behavior, but does not reduce mechanical hyperalgesia in a rodent model of inflammatory pain. Neuroscience letters. 2001;304(3):137-40.

Koch K. Assessing the impact of non-steroidal antiinflammatory drugs in the hot plate test: An alternative model. 2006.

Espejo EF, Stinus L, Cador M, Mir D. Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat. Psychopharmacology. 1994 Jan;113(3-4):500-10. PubMed PMID: 7862866. Epub 1994/01/01. eng.

Törnqvist L, Vartia P, Vartia YO. How should relative changes be measured? The American Statistician. 1985;39(1):43-6.

Vickers AJ. The use of percentage change from baseline as an outcome in a controlled trial is statistically inefficient: a simulation study. BMC Medical Research Methodology. 2001 June 28;1(1):6.

Kruk-Slomka M, Boguszewska-Czubara A, Slomka T, Budzynska B, Biala G. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands. Neural Plasticity. 2016;2016:15.

Passive Avoidance Task Behavioural and Functional sScience Laboratory. Stanford Medical. Available at:

Fuchs PN. Beyond reflexive measures to examine higher order pain processing in rats. Pain Research and Management. 2000;5(3):215-9.

Mauderli AP, Acosta-Rua A, Vierck CJ. An operant assay of thermal pain in conscious, unrestrained rats. Journal of neuroscience methods. 2000;97(1):19-29.

Sonika G, Manubala R, Deepak J. Comparative studies on anti-inflammatory activity of Coriandrum Sativum, Datura stramonium and Azadirachta Indica. Asian J Exp Biol Sci. 2010;1(1):151-4.

Suaudeau C, do-Rego JC, Costentin J. Modifications in avoidance reactions of mice, on a second exposure to the hot plate, resist to various amnesia-inducing treatments. Cognitive Brain Research. 2005;25(1):339-47.

Zhang L, Han K. How to Analyze Change from Baseline: Absolute or Percentage Change; 2009.

Kaiser L. Adjusting for baseline: change or percentage change? Statistics in medicine. 1989;8(10):1183-90.