Animal Models of Nociception DANIEL LE BARS, 1 MANUELA GOZARIU, AND SAMUEL W. CADDEN INSERM U-161, Paris, France (D.L.B.); Laboratoires UPSA Bristol-Myers-Squibb, La Grande Arche Nord, Paris La De ´fense, France (M.G.); and The Dental School, University of Dundee, Dundee, Scotland (S.W.C.) This paper is available online at http://pharmrev.aspetjournals.org Abstract .............................................................................. 598 I. Introduction ........................................................................... 598 II. Ethical problems ....................................................................... 601 III. Input and output: the stimulus and the response .......................................... 601 A. The stimulus ....................................................................... 602 1. Electrical stimulation ............................................................ 602 2. Thermal stimulation ............................................................. 603 3. Mechanical stimulation ........................................................... 606 4. Chemical stimulation............................................................. 606 5. The choice of stimulus parameters ................................................. 607 B. The response ....................................................................... 607 IV. Behavioral models of nociception ........................................................ 607 V. Use of short duration stimuli (“phasic pain”) .............................................. 608 A. Tests based on the use of thermal stimuli ............................................. 608 1. The tail-flick test ................................................................ 608 a. The tail-flick test using radiant heat ............................................ 609 b. The tail-flick test using immersion of the tail .................................... 610 2. The paw withdrawal test ......................................................... 610 3. The hot plate test ................................................................ 611 4. Tests using cold stimuli .......................................................... 611 B. Tests based on the use of mechanical stimuli .......................................... 611 C. Tests based on the use of electrical stimuli ............................................ 612 1. Use of long trains of electrical stimuli .............................................. 612 a. Electrical stimulation of the tail ................................................ 612 b. Electrical stimulation of the paw (and tail) ...................................... 612 2. Use of single shocks or very short trains of electrical stimuli ......................... 613 a. Stimulation of the tail ......................................................... 613 b. Stimulation of the dental pulp.................................................. 614 c. Stimulation of the limbs ....................................................... 615 VI. Tests based on the use of long duration stimuli (“tonic pain”) ............................... 617 A. Intradermal injections............................................................... 617 B. Intraperitoneal injections of irritant agents (the “writhing test”) ......................... 618 C. Stimulation of hollow organs ......................................................... 619 VII. Nociceptive tests and stimulus-response relationships ..................................... 620 VIII. Nociceptive tests and motor activity ..................................................... 621 A. Not all flexion reflexes are nociceptive ................................................ 621 B. Not all nociceptive reflexes are flexion reflexes ........................................ 622 C. Spinal shock ....................................................................... 623 D. Excitatory effects of opioids on motor activity .......................................... 623 IX. The sensitivity of the tests .............................................................. 624 A. Statement of the problem............................................................ 624 B. What types of fibers underlie the responses? .......................................... 624 C. What is the significance of measurements of reaction time when the stimulus intensity is increasing? ......................................................................... 628 1 Address for correspondence: Daniel Le Bars, INSERM U-161, 2, rue d’Ale ´sia 75014 Paris, France. E-mail: lebars@broca.inserm.fr 0031-6997/01/5304-597–652$3.00 PHARMACOLOGICAL REVIEWS Vol. 53, No. 4 Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics 134/932142 Pharmacol Rev 53:597–652, 2001 Printed in U.S.A 597 by guest on November 25, 2015 pharmrev.aspetjournals.org Downloaded from