title: A reassessment of stress-induced "analgesia" in the rat using an unbiased method.
abstract: An increased tail-flick latency to noxious heat during or after stress in the rodent is usually interpreted as a stress-induced reduction in pain sensitivity and often described as a form of stress-induced "analgesia." However, this measure is an indirect and flawed measure of the change in nociceptive threshold to noxious heat. A major confound of the latency measure is the initial temperature of the tail, which can drop down to room temperature during stress, the consequence of a marked sympathetically mediated vasoconstriction in the skin of the extremities. We addressed this issue with tail-flick tests during contextual fear using infrared thermography to monitor temperature changes and a CO2 laser to deliver the heat stimulus. The experiment revealed a 4.2°C increase of the nociceptive threshold, confirming a true antinociceptive effect. However, its contribution to the increased withdrawal latency was less than two-thirds (63.2%). Nearly one-third (32.2%) was due to the drop in tail temperature (4.4°C), which also slowed conduction along sensory fibers (2.2%, included in the 32.2%). The remaining 4.6% was due to an increase in decisional/motor latency. This new unbiased method establishes beyond doubt that a conditioned stress response is associated with true antinociception to noxious heat. It also confirms that stress-induced changes in skin temperature can be a major confound in tail-flick tests. The present study shows, for the first time, the exact contribution of these two components of the tail-flick latency for a stress response. Less than two-thirds of the increase in tail-flick latency to noxious heat, evoked by conditioned fear, reflects true antinociception. The remaining is due to skin vasoconstriction.
authors.affiliation: School of Medical Sciences, University of New South Wales, NSW 2052, Australia Department of Neurology, Moscow Medical Academy, Moscow 119021, Russia Team "Pain", INSERM UMRS 975, CNRS UMR 7225, Faculté de Médecine UPMC, Université Pierre et Marie Curie, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Carrive
authors.forename: Maxim
authors.initials: M
authors.lastname: Churyukanov
authors.forename: Daniel
authors.initials: D
authors.lastname: Le Bars
mesh_terms: D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal; D001703:Biophysics; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D005239:Fear; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy*; D007834:Lasers / Q000009:adverse effects; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*; D013817:Thermography / Q000379:methods