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A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans

Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

doi: 10.1097/j.pain.0000000000000515
Research Paper

The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P < 0.001). When expressed as force divided by circumference, baseline thresholds for 0.8 mm probes were higher than for 0.2 mm in both species (both P < 0.001) suggesting spatial summation. At similar probe diameters, ramped stimuli showed higher baseline thresholds than stepped stimuli (P < 0.01) but similar sensitivity to change. For ramped stimuli sensitivity to change was higher with small probe tips than large blunt tips in both pain models (P < 0.01 in rat, P < 0.05 in humans). These data show that rat paw withdrawal threshold to punctate stimuli (0.2 mm diameter) can be used as surrogate parameters for human mechanical pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure—the leading positive sensory sign after peripheral nerve injury in humans—is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

This study validates paw withdrawal to punctate (0.2 mm diameter) mechanical stimuli in rats as a model of mechanical hyperalgesia to the same stimuli in humans and emphasizes the importance of standardization of stimulus parameters.

aDepartment of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), University of Heidelberg, Mannheim, Germany

bInstitute of Medical Physiology “Richard Burian,” Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Corresponding author. Address: Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim (CBTM), University of Heidelberg, Ludolf-Krehl-Straβe 13, 68167 Mannheim, Germany. Tel.: 0049 (0)621 383 9637; fax: 0049 (0)621 383 9921. E-mail address: (O. Caspani).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received September 23, 2015

Accepted February 02, 2016

© 2016 International Association for the Study of Pain
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