A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour

Dunham, James P.; Hulse, Richard P.; Donaldson, Lucy F.

Abstract

Background

Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents.

New method

We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured.

Results

Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: −11.3 °C to −11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours.

Comparison

Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients.

Conclusion

Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain.

Citation

Dunham, J. P., Hulse, R. P., & Donaldson, L. F. (2015). A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour. Journal of Neuroscience Methods, 249, 29-40. https://doi.org/10.1016/j.jneumeth.2015.03.032

• Journal Article Type: Article
• Acceptance Date: Mar 30, 2016
• Online Publication Date: Apr 6, 2015
• Publication Date: 2015-07
• Deposit Date: Jan 5, 2017
• Publicly Available Date: Jan 5, 2017
• Journal: Journal of Neuroscience Methods
• Print ISSN: 0165-0270
• Electronic ISSN: 1872-678X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 249
• Pages: 29-40
• DOI: https://doi.org/10.1016/j.jneumeth.2015.03.032
• Keywords: Pain; Behaviour; Rat; Human; Cold; Nociception
• Public URL: https://nottingham-repository.worktribe.com/output/750147
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0165027015001338
• Additional Information: This article is maintained by: Elsevier; Article Title: A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour; Journal Title: Journal of Neuroscience Methods; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jneumeth.2015.03.032; Content Type: article; Copyright: Copyright © 2015 Published by Elsevier B.V.