Douleur et Analgésie

, Volume 14, Issue 1, pp 21–38 | Cite as

Regard critique sur les modèles animaux de douleur aiguë

  • D. Le Bars


Les modèles de douleur aiguë utilisés chez l’animal d’expérience au cours des études précliniques et dans la recherche «fondamentale» sont analysés de façon critique. Les rapports entre tests de douleur aiguë et motricité sont abordés sous différents angles, notamment l’influence que les ajustements posturaux de l’animal exercent sur une réponse motrice des membres et la signification des réflexes de flexion et d’extension. Il est souligné que les réflexes de flexion ne sont pas tous nociceptifs. Comme la plupart des tests ne permettent qu’une mesure de seuil alors que la douleur clinique en est toujours éloignée lorsque le médecin doit la prendre en charge, le problème de leur sensibilité se trouve posé. Certaines questions sont plus particulièrement développées, notamment (1) la signification des mesures de «latence» lorsque le stimulus est croissant et (2) la nature des fibres à l’origine de la réaction observée qui pourrait être différente selon que l’on stimule un territoire sain ou enflammé. La prédictivité de ces tests sur le plan clinique est passée en revue avec quelques exemples. Puis les facteurs pouvant perturber la mesure des réponses comportementales de l’animal sont analysés, notamment les interactions entre stimulus hétérotopiques, les facteurs environnementaux et les fonctions psychophysiologiques et psychologiques intercurrentes (phénomènes subjectifs «indésirables», phénomènes d’apprentissage). Les fonctions physiologiques intercurrentes (thermorégulation, vasomotricité, pression artérielle) sont plus particulièrement commentées. Ces dernières considérations invitent à replacer la nociception dans un cadre homéostatique plus vaste qui, outre la douleur, inclue d’autres fonctions comme l’anxiété et les fonctions végétatives. Enfin, la validité de certaines méthodes d’analyse des résultats est analysée.


The animal models of acute pain used in preclinical studies and «fundamental» research are analysed critically. We review the relationship between tests of acute pain and motor activity from a number of viewpoints; in particular we consider the influence which postural adjustments of the animal may exert on motor responses in the limbs and the significance of the flexor and extensor reflexes. It is emphasised that not all flexion reflexes are nociceptive. Since the majority of tests permit only a measurement of threshold, whereas clinical pain almost always lasts until the doctor deals with it, the problem of their sensitivity is put forward. Several questions are more particularly developed, namely (1) what significance do measurements of «latency» have when a stimulus is increasing; (2) what type(s) of fibres underlie the observed responses and might these be different depending on whether one is stimulating a healthy or an inflamed tissue. The predictivity of tests is illustrated with examples. Then, we review those factors which may distort behavioural measurements in animals, notably—interactions between heterotopics stimuli, environmental factors and related psychophysiological/psychological considerations (subjectively «undesirable» phenomena, learning phenomena). We pay particular attention to related physiological functions (thermoregulation, vasomotricity and blood pressure). These considerations lead us to re-position nociception within a much larger homeostatic framework which in addition to pain, includes phenomena such as anxiety and vegetative functions. Finally, we questioned the validity are some methods of analysing the results.


Acute pain behaviour reflexes Aδ-fibres C-fibres learning anxiety vegetative system 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adler M.W., Geller E.B., Rosow C.E. andCochin J.: The opioid system and temperature regulation.Ann. Rev. Pharmacol. Toxicol. 28, 429–449, 1988.CrossRefGoogle Scholar
  2. 2.
    Andrell O.: Cutaneous pain elicited in man by thermal radiation, dependence of the threshold intensity on stimulation time, skin temperature and analgesics.Acta. Pharmacol. Toxicol. 10, 30–37, 1954.Google Scholar
  3. 3.
    Ankier S.I.: New hot plate tests to quantify antinociceptive and narcotic antagonist activities.Eur. J. Pharmacol. 27, 1–4, 1974.PubMedCrossRefGoogle Scholar
  4. 4.
    Applebaum B.D. andHolzman S.G.: Stress-induced changes in the analgesic and thermic effects of opioid peptides in the rat.Brain Res. 358, 303–308, 1986.CrossRefGoogle Scholar
  5. 5.
    Auckland K. andWiig H.: Hemodynamics and interstitial fluid pressure in the rat tail.Amer. J. Physiol. Heart. Circ. Physiol. 247, H80-H87, 1984.Google Scholar
  6. 6.
    Baldwin A.E. andCannon J.T.: Sensitization of the tail-flick reflex following exposure to either a single prolonged test or behavioral testing under the analgesic influence of morphine.Pain 67, 163–172, 1996.PubMedCrossRefGoogle Scholar
  7. 7.
    Bandler R. andDepaulis A.:Midbrain periaqueductal gray control of defensive behavior in the cat and the rat. In: A. Depaulis and R. Bandler (eds): “The midbrain periasqueductal grey matter, functional, anatomical and neurochemical organization». NATO ASI series, vol. 213, 175–198, 1991.Google Scholar
  8. 8.
    Beecher H.K.: Limiting factors in experimental pain.J. Chron. Dis. 4, 11–21, 1956.PubMedCrossRefGoogle Scholar
  9. 9.
    Beecher H.K.: The measurement of pain.Pharmacol. Rev. 9, 59–209, 1957.PubMedGoogle Scholar
  10. 10.
    Behbehani M.M.: Functional characteristics of the midbrain periaqueductal gray.Progress in Neurobiology 46, 575–605, 1995.PubMedCrossRefGoogle Scholar
  11. 11.
    Behrends T., Schomburg E.D. andSteffens H.: Facilitatory interaction between cutaneous afferents from low threshold mechanoreceptors and nociceptors in segmental reflex pathways to alpha motoneurones.Brain Res. 260, 131–134, 1983.PubMedCrossRefGoogle Scholar
  12. 12.
    Benedetti C., Bonica J.J. andBelluci G.:Pathophysiology and therapy of postoperative pain, a review.In: «Advances in pain research and therapy» vol. 7, Benedetti C., Chapman C.R., Morrica G. (eds): New York, Raven Press, 373–407, 1984.Google Scholar
  13. 13.
    Berge O.G., Garcia-Cabrera I. andHole K.: Response latencies in the tail-flick test depend on tail skin temperature.Neurosc. Lett. 86, 284–288, 1988.CrossRefGoogle Scholar
  14. 14.
    Berry J.J., Montgomery L.D. andWilliams B.A.: Thermoregulatory responses of rats to varying environemental temperatures.Aviat. Space Environ Med. 55, 546–549, 1984.PubMedGoogle Scholar
  15. 15.
    Blessing WW: The lower brainstem and bodily homeostasis. Oxford University Press, 575 pp., 1997.Google Scholar
  16. 16.
    Bonnycastle D.D.:The use of animals in the study of analgetic drugs.In: «The assessment of pain in man and animal». Keele C.A. and Smith R. (eds), Livingston, Edimburgh, 231–243, 1962.Google Scholar
  17. 17.
    Brown A.C., Beeler W., Kloka A. andFields R.: Spatial summation of pre-pain and pain in human teeth.Pain 21, 1–16, 1985.PubMedCrossRefGoogle Scholar
  18. 18.
    Brunaud M.: Effets Pharmacologiques de la morphine et des morphiniques chez les animaux domestiques.Rec. Med. Vet. 162, 1421–1428, 1986.Google Scholar
  19. 19.
    Buettner K.: Effects of extreme heat and cold on human skin. II. Surface temperature, pain and heat conductivity in experiments with radiante heat.J. Applied. Physiol. 3, 703–713, 1951.Google Scholar
  20. 20.
    Bustamante D., Paeile C., Willer J.C. andLe Bars D.: Effects of intravenous non-steroidal anti-inflammatory drugs on a C-fibre reflex elicited by a wide range of stimulus intensities in the rat.J. Pharmacol. Exper. Ther. 276, 1232–1243, 1996.Google Scholar
  21. 21.
    Calcagnetti D.J. andHoltzman S.G.: Potentiation of morphine analgesia in rats given a single exposure to restraint stress immobilization.Pharmacol. Biochem. Behav. 41, 449–453, 1992.PubMedCrossRefGoogle Scholar
  22. 22.
    Calvino B.: Differential effect of a chemical algogen on two nociceptive thresholds.Physiology and Behavior 47, 907–910, 1990.PubMedCrossRefGoogle Scholar
  23. 23.
    Calvino B., Villanueva L. andLe Bars D.: The heterotopic effects of visceral pain, behavioural and electrophysiological approaches in the rat.Pain 20, 261–271, 1984.PubMedCrossRefGoogle Scholar
  24. 24.
    Campbell I.G., Carsten E. andWatkins L.R.: Comparison of human pain sensation and flexion withdrawal evoked by noxious radiant heat.Pain 45, 259–268, 1991.PubMedCrossRefGoogle Scholar
  25. 25.
    Campbell E., Bevan S. andDray A.:Clinical applications of capsaicin and its analogues.In: Wood J. (Ed), Capsaicin in the study of pain, Academic Press Limited, London, 255–272, 1993.Google Scholar
  26. 26.
    Carmody J.: Avoiding fallacies in nociceptive measurements.Pain 63, 136, 1995.PubMedCrossRefGoogle Scholar
  27. 27.
    Carrive P.:Functional organization of PAG neurons controlling regional vascular beds. In: A. Depaulis and R. Bandler (eds) «The midbrain periaqueductal grey matter, functional, anatomical and neurochemical organization». NATO ASI series,213, 67–100, 1991.Google Scholar
  28. 28.
    Carroll M.N.: The effect of injury in nociceptive tests employed in analgetic assays.Arch. Int. Pharmacodyn. Ther. 123, 48–57, 1959.PubMedGoogle Scholar
  29. 29.
    Carstens E. andAnsley D.: Hindlimb Flexion Withdrawal Evoked by Noxious Heat in Conscious Rats—Magnitude Measurement of Stimulus—Response Function, Suppression by Morphine and Habituation.J. Neurophysiol. 70, 621–629, 1993.PubMedGoogle Scholar
  30. 30.
    Carstens E. andCampbell I.G.: Parametric and Pharmacological studies of midbrain suppression of the hind limb flexion withdrawal reflex in the rat.Pain 33, 201–213, 1988.PubMedCrossRefGoogle Scholar
  31. 31.
    Carstens E. andWilson C.: Rat tail flick reflex, magnitude measurement of stimulus-response function, suppression by morphine and habituation.J. Neurophysiol. 70, 630–639, 1993.PubMedGoogle Scholar
  32. 32.
    Chapman C.R., Casey K.L., Dubner R., Foley K.M., Gracely R.H. andReading A.E.: Pain measurement, An overview.Pain 22, 1–31, 1985.PubMedCrossRefGoogle Scholar
  33. 33.
    Chapman D.N. andWay E.L.: Modification of endorphine/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator and an ionophore.Brit. J. Pharmacol. 75, 389–396, 1982.Google Scholar
  34. 34.
    Chau:Analgesic testing in animal models.In: “Pharmacological methods in the control of inflammation».In: Chang J.Y. and Lewis A.J. (eds), Alan Liss, New York, 195–212, 1989.Google Scholar
  35. 35.
    Chen X.H., Geller E.B., de Riel J.K., Liu-Chen L.Y. andAdler M.W.: Antisense oligodeoxynucleotides against mu- or kappa-opioid receptors block agonist-induced body temperature changes in rats.Brain Res. 688, 237–241, 1995.PubMedCrossRefGoogle Scholar
  36. 36.
    Conway E.L., Brown M.J. andDollery C.T.: Plasma catecholamine and cardiovascular responses to morphine and d-ala-d-leu-enkephelin in conscious rats.Arch. Int. Pharmacodyn. Ther. 265, 244–258, 1983.PubMedGoogle Scholar
  37. 37.
    Cook L. andWeidley E.: Behavioral effects of some psychopharmacological agents.Annals N.Y. Acad. Sci. 66, 740–752, 1957.CrossRefGoogle Scholar
  38. 38.
    Cooper B.Y. andVierck C.J.: Measurement of pain and morphine hyperalgesia in monkeys.Pain 26, 361–392, 1986.PubMedCrossRefGoogle Scholar
  39. 39.
    Cooper B.Y., Vierck C.J. Jr andYeomans D.C.: Selective reduction of second pain sensations by systemic morphine in humans.Pain 24, 93–116, 1986.PubMedCrossRefGoogle Scholar
  40. 40.
    D'Amore A., Chiarotti F. andRenzi P.: High intensity nociceptive stimuli minimize behavioral effects induced by restraining stress during the tail-flick test.J. Pharmacol. Toxicol. Methods 27, 197–201, 1992.PubMedCrossRefGoogle Scholar
  41. 41.
    Dalens B.: La douleur aiguë de l’enfant et son traitement.Ann. Fr. Anesth. Réanims. 10, 36–61, 1991.Google Scholar
  42. 42.
    Dewey W.L.:Narcotic-antagonist assay procedures in dogs.In: «Narcotic antagonists. Advances in Biochemical PsychoPharmacology», vol. 8, Braude M.C., Harris L.S., May E.L., Smith J.P. and Villareal J.E. (eds),Raven Press, New York, 263–272, 1974.Google Scholar
  43. 43.
    Dirig D.M. andYaksh T.L.: Differential right shifts in the dose-response curve for intratrathecal morphine and sufentanil as a function of stimulus intensity.Pain 62, 321–328, 1995.PubMedCrossRefGoogle Scholar
  44. 44.
    Dubinsky B., Gebre-Mariam S., Capetola R.J. andRosenthale M.E.: The antialgesic drugs, human therapeutic correlates of their potency in laboratory animal models of hyperalgesia.Agents and Actions 20, 50–60, 1987.PubMedCrossRefGoogle Scholar
  45. 45.
    Dubner R., Price D.D., Beitel R.E. andHu J.W.:Peripheral correlates of behavior in monkey and human related to sensory discriminative aspects of pain.In: D.J. Anderson and B. Matthews (eds), «Pain in the trigeminal region»,Elsevier, New York, 57–66, 1977.Google Scholar
  46. 46.
    Dubuisson D. andDennis S.G.: The formalin test, a quantitative study of the analgesic effects of morphine, meperidine and brain stem stimulation in rats and cats.Pain 4, 161–174, 1977.PubMedCrossRefGoogle Scholar
  47. 47.
    Duggan A.W., Griersmith B.T., Headley P.M. andMaher J.B.: The need to control skin temperature when using radiant heat in test of analgesia.Exper. Neurol. 61, 471–478, 1978.CrossRefGoogle Scholar
  48. 48.
    Eide P.K. andTjolsen A.: Effects of serotonin receptor antagonists and agonists on the tail-flick response in mice involve altered tailskin temperature.Neuropharmacology 27, 889–893, 1988.PubMedCrossRefGoogle Scholar
  49. 49.
    Evans A.G.J., Nasmyth P.A. andStewart H.C.: The fall of blood pressure caused by intravenous morphine in the rat and the cat.Brit. J. Pharmacol. 7, 542–552, 1952.PubMedGoogle Scholar
  50. 50.
    Falcon F., Guendellman D., Stolberg A., Frenk H. andUrca G.: Development of thermals nociception in rats.Pain 67, 203–208, 1996.PubMedCrossRefGoogle Scholar
  51. 51.
    Fennessy M.R. andRattray J.F.: Cardiovascular effects of intravenous morphine in the anaesthetized rat.Eur. J. Pharmacol. 14, 1–8, 1971.PubMedCrossRefGoogle Scholar
  52. 52.
    Fields H., Bry J., Hentall I. andZorman G.: The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat.J. Neurosci. 3, 2545–2552, 1983.PubMedGoogle Scholar
  53. 53.
    Fitzgerald M.:Neurobiology of fetal and neonatal pain.In: «Textbook of Pain» P.D. Wall and R. Melzack (eds), Churchill Livingstone, Edinburgh, 153–163, 1994.Google Scholar
  54. 54.
    Fleischer E., Handwerker H.O. andJounkhadar S.: Unmyelinated nociceptive units in two skin areas of the rat.Brain Res. 267, 81–92, 1983.PubMedCrossRefGoogle Scholar
  55. 55.
    Franklin K.B.J. andKelly S.J.: Sympathetic control of tryptophane uptake and morphine analgesia in stressed rats.Eur. J. Pharmacol. 126, 145–150, 1986.PubMedCrossRefGoogle Scholar
  56. 56.
    Furer M. andHardy J.D.: The reaction to pain as determined by the galvanic skin response.Proc. Ass. Res. Nerv. Dis. 29, 72–89, 1950.Google Scholar
  57. 57.
    Gemmel R.T. andHales J.R.S.: Cutaneous arteriovenous anastomoses present in the rat tail but absent from the ear of the rat.J. Anat. 124, 355–358, 1977.Google Scholar
  58. 58.
    Gibbs N.M., Larach D.R., Skeehan T.M. andSchuler H.G.: Halothane induces depressor responses to noxious stimuli in the rat.Anesthesiology 70, 503–510, 1989.PubMedCrossRefGoogle Scholar
  59. 59.
    Gomes C., Svensson T.H. andTrolin G.: Evidence for the involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat.J. Neural. Transm. 39, 33–46, 1976.PubMedCrossRefGoogle Scholar
  60. 60.
    Gomes C., Svensson T.H. andTrolin G.: Effects of morphine on central catecholamine turnover, blood pressure and heart rate in the rat.Naunyn Smiederberg’s Arch. Pharmacol. 294, 141–147, 1976.CrossRefGoogle Scholar
  61. 61.
    Granat F.R. andSaelens J.K.: Effect of stimulus intensity on the potency of some anagetic agents.Arch. Int. Pharmacodyn. Ther. 205, 52–60, 1973.PubMedGoogle Scholar
  62. 62.
    Gray W., Osterberg A. andScuto T.: Measurement of the analgesic efficacy and potency of pentazocine by the d’amour and smith method.J. Pharmacol. Exper. Ther. 172, 154–162, 1970.Google Scholar
  63. 63.
    Guirimand F., Strimbu-Gozariu M., Willer J.C. andLe Bars D.: Effects of mu, delta and kappa antagonists on the depression of a C-fiber reflex by intrathecal morphine and DAGO in the rat.J. Pharmacol. Exper. Ther. 269, 1007–1020, 1994.Google Scholar
  64. 64.
    Guirimand F., Chauvin M., Willer J.C. andLe Bars D.: Effects of intravenous morphine and buprenorphine upon a C-fibre reflex in the rat.J. Pharmacol. Exper. Ther. 273, 830–841, 1995.Google Scholar
  65. 65.
    Hammond D.L.:Inference of pain and its modulation from simple behaviors.In: «Issues In Pain Management» Chapman C.R. and Loeser J.D. (eds):Raven Press, New York, 69–91, 1989.Google Scholar
  66. 66.
    Hamon I.: Voies anatomiques de la douleur chez le nouveau-né prématuré.Arch. Pédriatr. 3, 1006–1012, 1996.CrossRefGoogle Scholar
  67. 67.
    Han J.S. andRen M.F.: The importance of monitoring tail-skin temperature in measuring tail-flick latency.Pain 46, 117, 1991.PubMedCrossRefGoogle Scholar
  68. 68.
    Handwerker H.O. andKobal G.: Psychophysiology of experimentally induced pain.Physiol. Rev. 73, 639–671, 1993.PubMedGoogle Scholar
  69. 69.
    Hardy J.D.: Threshold of pain and reflex contraction as related to noxious stimuli.J. Applied. Physiol. 5, 725–739, 1953.Google Scholar
  70. 70.
    Hardy J.D.: Body temperature regulation.In: «Medical physiology», vol. 2, V. Mountcastle (ed), Mosby, St Louis, 1417–1456, 1980.Google Scholar
  71. 71.
    Hardy J.D., Wolff H.G. andGoodell H.: Studies on pain. A new method for measuring pain threshold, observation on spatial summation of pain.J. Clin. Invest. 19, 649–657, 1940.PubMedCrossRefGoogle Scholar
  72. 72.
    Hardy J.D., Wolff H.G. andGoodell H.: The pain threshold in man.Proc. Ass. Res. Nerv. Dis. 23, 1–15, 1943.Google Scholar
  73. 73.
    Hardy J.D., Wolff H.G. andGoodell H.:Pain sensation and reaction. Williams and Wilkins, Baltimore, 435 pp., 1952.Google Scholar
  74. 74.
    Hardy J.D., Hammel H.T. andMurgatroyd D.: Spectral transmittance and reflectance of excised human skin.J. Appl. Physiol. 9, 257–264, 1956.PubMedGoogle Scholar
  75. 75.
    Hardy J.D., Stoll A.M., Cunningham D., Benson W.M. andGreene L.: Resonses of the rat to thermal radiation.Am. J. Physiol. 189, 1–5, 1957.PubMedGoogle Scholar
  76. 76.
    Hargreaves K., Dubner R., Brown F., Flores C. andJoris J.: A new and sensitive method for measuring thermal nociception in cutaneus hyperalgesia.Pain 32, 77–88, 1988.PubMedCrossRefGoogle Scholar
  77. 77.
    Harris L.S. andPierson A.K.: Some narcotic antagonists in the benzomorphan series.J. Pharmacol. Exper. Ther. 143, 141–148, 1964.Google Scholar
  78. 78.
    Hayes R.L., Bennet G.J., Newlon P.G. andMayer D.J.: Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli.Brain Res. 155, 69–90, 1978.PubMedCrossRefGoogle Scholar
  79. 79.
    Hendershot L.C. andForsaith J.: Antagonism of the frequency of phenylquinone-induced writhing in the mouse by weak analgesics and non-analgesics.J. Pharmacol. Exper. Ther. 125, 237–240, 1959.Google Scholar
  80. 80.
    Hill H.E., Belleville R.E. andWikler A.: Reduction of pain-conditioned anxiety by analgesic doses of morphine in rats.Proc. Soc. exp. Biol. 86, 881–884, 1954.Google Scholar
  81. 81.
    Hitchens J.T., Goldstein S., Shemano I. andBeiler J.M.: Analgesic effects of irritants in threee models of experimentally-induced pain.Arch. Int. Pharmacodyn. 169, 384–393, 1967.PubMedGoogle Scholar
  82. 82.
    Holmberg H. andSchouenborg J.: Postnatal development of the nociceptive withdrawal reflexes in the rat, a behavioural and electromyographic study.J. Physiol. 493, 239–252, 1996.PubMedGoogle Scholar
  83. 83.
    Holtzman S.G.: Effects of morphine and narcotic antagonists on avoidance behavior in the squirrel monkey.J. Pharmaco. Exp. Ther. 196, 145–155, 1978.Google Scholar
  84. 84.
    Holzer P.: Capsaicin, cellular targets, mechanisms of action, and selectivity for thin sensory neurons.Pharmacol. Rev. 43, 143–201, 1991.PubMedGoogle Scholar
  85. 85.
    Hunskaar H.S., Berge O.G. andHole K.: A modified hot-plate test sensitive to mild analgesics.Behav. Brain Res. 21, 101–108, 1986.PubMedCrossRefGoogle Scholar
  86. 86.
    Illitch P.A., King T.E. andGrau J.W.: Impact of shock on pain reactivity, I Whether hypo- or hyperalgesia is observed depends on how pain reactivity is tested.Animal Behavior Processes 21, 331–347, 1995.CrossRefGoogle Scholar
  87. 87.
    Jackson H.: The evaluation of analgesic potency of drugs using thermal stimulation in the rat.Br. J. Pharmacol. 7, 196–203, 1952.Google Scholar
  88. 88.
    Jensen R.A., Messing R.B., Spielher V.R., Martinez J.L. Jr,Vasquez B.J. andMcGaugh J.L.: Memory, opiate receptors and aging.Peptides 1, 197–201, 1980.CrossRefGoogle Scholar
  89. 89.
    Jensen T.S. andYaksh T.L.: Comparison of the antinociceptive action of morphine in the periaqueductal gray, medial and paramedial medulla in the rat.Brain Res. 363, 99–113, 1986.PubMedCrossRefGoogle Scholar
  90. 90.
    Jourdan D., Ardid D., Chapuy E., Eschalier A. andLe Bars D.: Audible and ultrasonic vocalization elicited by single electrical nociceptive stimuli to the tail in the rat.Pain 63, 237–249, 1995.PubMedCrossRefGoogle Scholar
  91. 91.
    Jourdan D., Ardid D., Chapuy Le Bars D. andEschalier A.: Effect of analgesics on audible and ultrasonic pain-induced vocalization in the rat.Life Sci. 63, 1761–1768, 1998.PubMedCrossRefGoogle Scholar
  92. 92.
    Jurna I. andHeinz G.: Differential effects of morphine and opioid analgesics on A and C fiber-evoked activity in ascending axons of the rat spinal cord.Brain Res. 171, 573–576, 1979.PubMedCrossRefGoogle Scholar
  93. 93.
    Kallina C.F. andGrau J.W.: Tail-flick test-I Impact of a suprathreshold exposure to radiant heat on pain reactivity in rats.Physiol. Behav. 58, 161–168, 1995.PubMedCrossRefGoogle Scholar
  94. 94.
    Kayser V. andGuilbaud G.: The analgesic effects of morphine but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats.Brain Res. 267, 131–138, 1983.PubMedCrossRefGoogle Scholar
  95. 95.
    Kelly D.D.: The role of endorphins in stress-induced analgesia.Ann. New York Acad. Sci. 398, 260–271, 1982.CrossRefGoogle Scholar
  96. 96.
    Kelly S.J. andFranklin K.B.J.: Evidence that stress augments morphine analgesia by increasing brain tryptophan.Neurosci. Lett. 44, 305–310, 1984.PubMedCrossRefGoogle Scholar
  97. 97.
    Kelly S.J. andFranklin K.B.J.: Electrolytic raphe magnus lesions blocks analgesia induced by a stress-morphine interaction but not analgesia induced by morphine alone.Neurosci. Lett. 52, 147–152, 1984.PubMedCrossRefGoogle Scholar
  98. 98.
    Khan A.A., Raja S.N., Manning D.C., Campbell J.N. andMeyer R.A.: The effects of bradykinin and sequence-related analogs on the response properties of cutaneous nociceptors in monkeys.Somatosensory and Motor Res. 9, 97–106, 1992.Google Scholar
  99. 99.
    Kirkwood P.A., Schomburg E.D. andSteffens H.: Facilitatory interactions in spinal reflex pathways from nociceptive cutaneous afferents and identified secondary spindle afferents in the cat.Exp. Brain Res. 68, 657–660, 1987.PubMedCrossRefGoogle Scholar
  100. 100.
    Kiyatkin E.A.: Nociceptive sensitivity/behavioural reactivity regulation during aversive states of different nature, its mediation by opioid peptides.Int. J. Neurosci. 44, 91–110, 1989.PubMedGoogle Scholar
  101. 101.
    Kiyatkin E.A.: Neurobiological background of pain and analgesia, the attempt at revaluation according to position of the organism’s adaptative activity.Int. J. Neurosci. 52, 125–188, 1990.PubMedCrossRefGoogle Scholar
  102. 102.
    Komisaruk B.R. andWallman J.: Antinociceptive effects of vaginal stimulation in rats, neurophysiological and behavioral studies.Brain Res. 137, 85–107, 1977.PubMedCrossRefGoogle Scholar
  103. 103.
    Kornetsky C.: Effects of anxiety and morphine on the anticipation and perception of painful radiant thermal stimuli.J. Comp. Physiol. Psychol. 47, 130–132, 1954.PubMedCrossRefGoogle Scholar
  104. 104.
    Kraus E. andLe Bars D.: Morphine antagonizes inhibitory controls of nociceptive reactions, triggered by visceral pain in the rat.Brain Res. 379, 151–156, 1986.PubMedCrossRefGoogle Scholar
  105. 105.
    Kraus E., Besson J.M. andLe Bars D.: Behavioral model for Diffuse Noxious Inhibitory Controls, DNIC:, potentiation by 5-hydroxytryptophan.Brain Res. 231, 461–465, 1982.PubMedCrossRefGoogle Scholar
  106. 106.
    Kraus E., Le Bars D. andBesson J.M.: Behavioral confirmation of «Diffuse Noxious Inhibitory Controls», DNIC: and evidence for a role of endogenous opiates.Brain Res. 206, 495–499, 1981.PubMedCrossRefGoogle Scholar
  107. 107.
    Labrecque G., Vanier M.C.: Biological rhythms in pain and in the effects of opioid analgesics.Pharmacol. and Therap. 68, 129–147, 1995.CrossRefGoogle Scholar
  108. 108.
    Lai Y.Y. andChan S.H.H.: Shortened pain response time following repeated algesiometric test in rats.Physiol. and Behav. 28, 1111–1113, 1982.CrossRefGoogle Scholar
  109. 109.
    Laska E.M., Sunshine A., Wanderling J.A. andMeisner M.J.: Quantitative differences in aspirin analgesia in three models of clinical pain.J. Clin. Pharmacol. 22, 531–542, 1982.PubMedCrossRefGoogle Scholar
  110. 110.
    Le Bars D., Calvino B., Villanueva L. andCadden S.:Physiological approaches to counter-irritation phenomena.In: «Stress-induced analgesia», Tricklebank M.D. and Carzon G. (eds): John Wiley, New-York, 67–101, 1984.Google Scholar
  111. 111.
    Le Bars D., Guilbaud G., Jurna I. andBesson J.M.: Differential effects of morphine on response of dorsal horn lamina V type cells elicited by A and C fibre stimulation in the spinal cat.Brain Res. 115, 518–524, 1976.PubMedCrossRefGoogle Scholar
  112. 112.
    Le Bars D., Willer J.C., De Broucker T. andVillanueva L.:Neurophysiological mechanisms involved in the pain-relieving effects of counter-irritation and related techniques.In: «Scientific basis of acupuncture», B. Pomerantz and G. Stüx (eds), Springer Berlin, 79–112, 1989.Google Scholar
  113. 113.
    Le Bars D., Gozariu M. andCadden S.W.: L’évaluation de la douleur aiguë chez l’animal d’expérience.Ann. Fr. Anesth. Réanim., sous presse.Google Scholar
  114. 114.
    Lichtman A.H., Smith F.L. andMartin B.R.: Evidence that the antinociceptive tail-flick response is produced independently from changes in either tail-skin temperature or core temperature.Pain 55, 283–295, 1993.PubMedCrossRefGoogle Scholar
  115. 115.
    Lipkin M. andHardy J.D.: Measurement of some thermal properties of human tissues.J. Applied. Physiol. 7, 212–217, 1954.Google Scholar
  116. 116.
    Lloyd-Thomas A.R. andFitzgerald M.: Do fetuses feel pain? Reflex responses do not necessarily signify pain.Brit. Med. J. 313, 797–798, 1996.PubMedGoogle Scholar
  117. 117.
    Loux J.J., Smith S. andSalem H.: Comparative analgesic testing of various compounds in mice using writhing techniques.Arzneim Forsch 28, 1644–1647, 1978.Google Scholar
  118. 118.
    Lovick T.A.: Central nervous system integration of pain control and autonomic function.News in Physiol. Sci. 6, 82–86, 1991.Google Scholar
  119. 119.
    Lovick T.A.:Integrated activity of cardiovascular and pain regulatory role in adaptative behavioural responses.Progress in Neurobiology 40, 631–644, 1993.PubMedCrossRefGoogle Scholar
  120. 120.
    Lundberg A.:Inhibitory control from the brain stem of transmission from primary afferents to motoneurons, primary afferent terminals and ascending pathways.In: “Brain Stem Control of Spinal Mechanisms», Sjölund B. and Björklund A. (eds),Elsevier, Amsterdam, 179–224, 1982.Google Scholar
  121. 121.
    Luttinger D.: Determination of antinociceptive efficacy of drugs in mice using different water temperatures in a tail immersion test.J. Pharmacol. Methods 13, 351–357, 1985.PubMedCrossRefGoogle Scholar
  122. 122.
    Lynn B.: Capsaicin, actions on nociceptive C-fibres and therapeutic potential.Pain 41, 61–69, 1990.PubMedCrossRefGoogle Scholar
  123. 123.
    Lynn B. andBaranowski R.: A comparison of the relative numbers and properties of cutaneous nociceptive afferents in different mammalian species. In: «Fine afferent nerve fibers and pain», R.F. Schmidtet al. (eds), Weinheim VCH, 86–94, 1987.Google Scholar
  124. 124.
    McMahon S. andKoltzenburg M.: The changing role of primary afferent neurones in pain.Pain 43, 269–272, 1990.PubMedCrossRefGoogle Scholar
  125. 125.
    Meyer R.A., Campbell J.N. andRaja S.N.: Peripheral neural mechanisms of nociception. In: «Textbook of pain» P.D. Wall and R. Melzack (eds), Churchill Livingston, 1994, 13–44, 1980.Google Scholar
  126. 126.
    Milne R.J. andGamble G.D.: Habituation to sham testing procedures modifies tail-flick latencies, effects on nociception rather than vasomotor tone.Pain 39, 103–107, 1989.PubMedCrossRefGoogle Scholar
  127. 127.
    Mitchell D. andHellon R.F.: Neuronal and behavioral responses in rats during noxious stimulation of the tail.Proc. Roy. Soc. B 177, 169–194, 1977.CrossRefGoogle Scholar
  128. 128.
    Montagne-Clavel J. andOliveras J.L.: The «plantar test» apparatus, Ugo Basile Biological Apparatus:, a controlled infrared noxious radiant heat stimulus for precise withdrawal latency measurement in the rat, as a tool for humans?Somatosensory and Motor Research. 13, 215–223, 1996.PubMedCrossRefGoogle Scholar
  129. 129.
    Ness T.J. andGebhart G.F.: Centrifugal modulation of the rat tail flick reflex evoked by graded noxious heating.Brain Res. 386, 41–52, 1986.PubMedCrossRefGoogle Scholar
  130. 130.
    O'Callaghan J.P. andHolzman S.G.: Quantification of the analgesic activity of narcotic antagonists by a modified hot plate procedure.J. Pharmacol. Exper. Ther. 192, 497–505, 1975.Google Scholar
  131. 131.
    Ochoa J. andMair W.G.: The normal sural nerve in man. I. Ultrastructure and numbers of fibres and cells.Acta Neuropathologica. 13, 197–216, 1969.PubMedCrossRefGoogle Scholar
  132. 132.
    Paalzow G. andPaalzow L.: Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine.Psychopharmacologia 45, 9–20, 1975.CrossRefGoogle Scholar
  133. 133.
    Pircio A.W., Fedele C.T. andBierwagen M.E.: A new method for adjuvant induced arthritis in the rat.Eur. J. Pharmacol. 31, 207–215, 1975.PubMedCrossRefGoogle Scholar
  134. 134.
    Pong S.F., Demuth S.M., Kinney C.M. andDeegan P.: Prediction of human analgesic dosages of nonsteroidal anti-inflammatory drugs, NSAIDs: from analgesic ED50 values in mice.Arch. Pharmacodyn. Therap. 273, 212–220, 1985.Google Scholar
  135. 135.
    Price D.D. andBarber J.: An analysis of factors that contribute to the efficacy of hypnotic analgesia.J. Abnorm. Psychol. 96, 46–51, 1987.PubMedCrossRefGoogle Scholar
  136. 136.
    Price D.D., Von Der Gruen A., Miller J. andRafii A.: A psychophysical analysis of morphine analgesia.Pain 22, 261–269, 1985.PubMedCrossRefGoogle Scholar
  137. 137.
    Rand R.P., Burton A.C. andIng T.: The tail of the rat, in temperature regulation and acclimatation.Can. J. Physiol. Pharmacol. 43, 257–267, 1965.PubMedGoogle Scholar
  138. 138.
    Randall L.O. andSelitto J.J.: A method for measurement of analgesic activity on inflammed tissue.Arch. Int. Pharmacodyn. Ther. 111, 409–419, 1957.PubMedGoogle Scholar
  139. 139.
    Randich A. andMaixner W.: Interactions between cardiovascular and pain regulatory systems.Neurosci. Biobehav. Rev. 8, 343–367, 1984.PubMedCrossRefGoogle Scholar
  140. 140.
    Randich A., Thurston C.L., Ludwig P.S., Timmerman M.R. andGebhart G.F.: Antinociception and cardiovascular responses produced by intravenous morphine, the role of vagal afferents.Brain Res. 543, 256–270, 1991.PubMedCrossRefGoogle Scholar
  141. 141.
    Rey R.: Histoire de la douleur. La découverte, Paris, 1993.Google Scholar
  142. 142.
    Ren M.F. andHan J.S.: Rat tail flick acupuncture analgesia.Chin. Med. J. 92, 576–582, 1979.Google Scholar
  143. 143.
    Romer D.: Pharmacological evaluation of mild analgesics.Br. J. Clin. Pharmacol. 10 Suppl. 2, 47S-251S, 1980.Google Scholar
  144. 144.
    Rosland J.H.: The formalin test in mice, the influence of ambient temperature.Pain 45, 211–216, 1991.PubMedCrossRefGoogle Scholar
  145. 145.
    Sandkkühler J., Treier A.C., Liu X.G. andOhnimus M.: The massive expression of c-fos protein in spinal dorsal horn neurons is not followed by long-term changes in spinal nociception.Neuroscience 73, 657–666, 1996.CrossRefGoogle Scholar
  146. 146.
    Sato A., Sato Y., Shimada F. andTorigata Y.: Varying changes in heart rate produced by nociceptive stimulation of the skin in rats at different temperatures.Brain Res. 110, 301–311, 1976.PubMedCrossRefGoogle Scholar
  147. 147.
    Sato A., Sato Y. andSchmidt R.F.: The impact of somatosensory input on autonomic functions.Rev. Physiol. Biochemi. Pharmacol. 130, 1–328, 1997.CrossRefGoogle Scholar
  148. 148.
    Scadding J.W.: The permanent anatomical effects of neonatal capsaicin on somatosensory nerves.J. Anatomy 131, 471–482, 1980.Google Scholar
  149. 149.
    Schmidt R.F. The articular polymodal nociceptor in health and disease.Progress. Brain Res. 113, 53–81, 1996.CrossRefGoogle Scholar
  150. 150.
    Schmidt R.F., Schaible H.G., Messlinger K., Heppelmann B., Hanesch U. andPawlak K.:Silent and active nociceptors, structures, functions and clinical implications.In: «Progress in pain research and management». Proceedings of 7th World Congress on Pain, vol. 2, Gebhart G.F., Hammond D.L. and Jensen T.S. (eds),IASP Press, Seattle, 213–250, 1994.Google Scholar
  151. 151.
    Schoenenfeld A.D., Lox C.D., Chen C.H. andLutherer L.O.: Pain threshold changes induced by acute exposure to altered ambient temperature.Peptides 6, 19–22, 1985.CrossRefGoogle Scholar
  152. 152.
    Schomburg E.D.: Spinal sensorimotor systems and their supraspinal control.Neurosci. Res. 7, 265–340, 1990.PubMedCrossRefGoogle Scholar
  153. 153.
    Schomburg E.D.: Restrictions on the interpretation of spinal reflex modulation in pain and analgesia research.Pain Forum 6, 101–109, 1997.Google Scholar
  154. 154.
    Schulze G.E. andPaul M.G.: Effects of morphine sulfate on operant behavior in Rhesus monkey.Pharmacol. Biochem. Behav. 38, 77–83, 1991.PubMedCrossRefGoogle Scholar
  155. 155.
    Shaw J.S., Rourke J.D. andBurns K.M.: Differential sensitivity of antinociceptive tests to opioid agonists and partial agonists.Br. J. Pharmacol. 95, 578–584, 1988.PubMedGoogle Scholar
  156. 156.
    Shimizu T.: Tooth pre-pain sesation elicited by electrical stimulation.J. Dent. Res. 43, 467–475, 1964.PubMedGoogle Scholar
  157. 157.
    Siegmund E., Cadmus R. andLu G.: Screening analgesics, including aspirin-type compound, based on the antagonism of chemically induced «writhing» in mice.J. Pharmacol. Exp. Therap. 119, 184–193, 1957.Google Scholar
  158. 158.
    Smith G.M. andBeecher H.K.: Measurement of «mental clouding» and other subjective effects of morphine.J. Pharmacol. Exp. Ther. 126, 5–62, 1959.Google Scholar
  159. 159.
    Steffens H. andSchomburg E.D.: Convergence in segmental reflex pathways from nociceptive and non-nociceptive afferents to alphamotoneurones in the cat.J. Physiol. 466, 191–211, 1993.PubMedGoogle Scholar
  160. 160.
    Stein E.A.: Morphine effects on the cardiovascular system of awake, freely behaving rats.Arch. Intern. Pharmacodyn. Therap. 223, 54–63, 1976.Google Scholar
  161. 161.
    Stolwijk J.A.J. andHardy J.D.: Skin and subcutaneous temperature changes during exposure to intense thermal radiation.J. Applied. Physiol. 20, 1006–1013, 1965.Google Scholar
  162. 162.
    Suh H.H., Fujimoto J.M. andTseng L.F.: Different radiant heat intensities differentiate intracerebroventricular morphine- from ß-endorphine-induced inhibition of the tail-flick response in the mouse.Eur. J. Pharmacol. 213, 337–341, 1992.PubMedCrossRefGoogle Scholar
  163. 163.
    Szolcsányi J.:Actions of capsaicin on sensory receptors.In: «Capsaicin in the study of pain», Wood J. (Ed) Academic Press, London, 1–26, 1993.Google Scholar
  164. 164.
    Taber RI:Predictive value of analgesic assays in mice and rats.In: «Narcotic antagonists», Advances in Biochemical PsychoPharmacology, vol. 8, Braude M.C., Harris L.S., May E.L., Smith J.P. and Villareal J.E. (eds).Raven Press, New York, 191–211, 1974.Google Scholar
  165. 165.
    Taber R.I., Greenhouse D.D. andIrwin S.: Inhibition of phenylquinone-induced writhing by narcotic antagonists.Nature 204, 189–190, 1964.PubMedCrossRefGoogle Scholar
  166. 166.
    Thurston C.L., Starnes A. andRandich A.: Changes in nociception, arterial blood pressure and heart rate produced by intravenous morphine in the conscious rat.Brain Res. 612, 70–77, 1993.PubMedCrossRefGoogle Scholar
  167. 167.
    Tjolsen A. andHole K.: The effect of morphine on core and skin temperature in rats.Neuroreport 3, 512–514, 1992.PubMedCrossRefGoogle Scholar
  168. 168.
    Tjolsen A. andHole K.:Animal models of analgesia.In: The Pharmacology of Pain, edited by A. Dickenson and J.M. Besson, Handbook of Experimental Pharmacology,Springer-Verla, 1–20, 1997.Google Scholar
  169. 169.
    Tjolsen A., Lund A., Eide P.K., Berge O.G. andHole K.: The apparent hyperalgesic effect of a serotonin antagonist in the tail flick test is mainly due to increased tail skin temperature.Pharmacol. Biochem. Behav. 32, 691–605, 1988.Google Scholar
  170. 170.
    Tjolsen A., Berge O.G., Hunskaar S., Rosland J.H. andHole K.: The formalin test, an evaluation of the method.Pain 51, 5–17, 1992.PubMedCrossRefGoogle Scholar
  171. 171.
    Tjolsen A., Lund A., Eide P.K., Berge O.G. andHole K.: An improved method for tail-flick testing with adjustment for tail-skin temperature.J. Neurosci. Methods 26, 259–265, 1989.PubMedCrossRefGoogle Scholar
  172. 172.
    Tjolsen A., Rosland J.H., Berge O.G. andHole K.: The increasing temperature hot plate test, an improved test of nociception in mice and rats.J. Pharmacol. Methods 25, 241–250, 1991.PubMedCrossRefGoogle Scholar
  173. 173.
    Tsuruoka M., Matsui A. andMatsui Y.: Quantitative relationship between the stimulus intensity and the response magnitude in the tail flick reflex.Physiol. Behav. 43, 79–63, 1988.PubMedCrossRefGoogle Scholar
  174. 174.
    Vidal C., Suaudeau C. andJacob J.: Regutation of body temperature and nociception induced by non-noxious stress in rat.Brain Res. 297, 1–10, 1984.PubMedCrossRefGoogle Scholar
  175. 175.
    Vierck C.J. andCooper B.Y.: Guideline for assessing pain reactions and pain modulation in laboratory animal subjects.In: Advances in pain research and therapy, vol. 6,Raven press, Kruger L. and Liebeskind J.C. (eds), New York, 305–322, 1984.Google Scholar
  176. 176.
    Vierck C.J. andCooper B.Y.: Vocalization as measures of pain in monkeys.Pain 26, 393–407, 1986.PubMedCrossRefGoogle Scholar
  177. 177.
    Willette R.N. andSapru H.N.: Peripheral versus central cardiorespiratory effects of morphine.Neuropharmacology 21, 1019–1026, 1982.PubMedCrossRefGoogle Scholar
  178. 178.
    Winder C.V., Pfeiffer C.C. andMaison G.L.: The nociceptive contraction of the cutaneous muscle of the guinea pig as elicited by radiant heat with observations on the mode of action of morphine.Arch. Int. Pharmacodyn. 72, 329–359, 1946.Google Scholar
  179. 179.
    Winter C.A. andFlakater L.: The relation between skin temperature and the effect of morphine upon the response to thermal stimuli in the albino rat and the dog.J. Pharmacol. 109, 183–188, 1953.Google Scholar
  180. 180.
    Winter C.A. andFlakater L.: Nociceptive thresholds as affected by parenteral administration of irritants and of various antinociceptive drugs.J. Pharmacol. Exper. Ther. 148, 373–379, 1965.Google Scholar
  181. 181.
    Winter J., Bevan S. andCampbell E.A.: Capsaicin and pain mechanisms.Br. J. Anaesth. 75, 157–168, 1995.PubMedGoogle Scholar
  182. 182.
    Yarnitsky D. andOchoa J.L.: Studies of pain sensation in man, perception thresholds, rate of stimulus rise and reaction time.Pain 40, 85–91, 1990.PubMedCrossRefGoogle Scholar
  183. 183.
    Yeomans D.C. andProudfit H.K.: Characterization of the foot withdrawal response to noxious radiant heat in the rat.Pain 59, 85–94, 1994.PubMedCrossRefGoogle Scholar
  184. 184.
    Yeomans D.C., Proudfit H.K.: Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat, electrophysiological evidence.Pain 68, 141–150, 1996.PubMedCrossRefGoogle Scholar
  185. 185.
    Yeomans D.C., Cooper B.Y. andVierck C.J.: Effects of systemic morphine on responses of primates to first or second pain sensations.Pain 66, 253–263, 1996.PubMedCrossRefGoogle Scholar
  186. 186.
    Yeomans D.C., Pirec V. andProudfit H.K.: Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat, behavioral evidence.Pain 68, 133–140, 1996.PubMedCrossRefGoogle Scholar
  187. 187.
    Young A.A. andDawson N.J.: Evidence for on-off control of heat dissipation from the tail of the rat.Can. J. Physiol. Pharmacol. 60, 392–398, 1982.PubMedGoogle Scholar
  188. 188.
    Zachariou V., Goldstein B.D. andYeomans D.C.: Low but not high rate noxious radiant skin heating evokes a capsaicin-sensitive increase in spinal cord dorsal horn release of substance P.Brain Res. 752, 143–150, 1997.PubMedCrossRefGoogle Scholar
  189. 189.
    Zamir N. andMaixner W.: The relationship between cardiovascular and pain regulatory systems.Ann. NY. Acad. Sci. 467, 371–384, 1986.PubMedCrossRefGoogle Scholar
  190. 190.
    Zimet P.O., Wynn R.L., Ford R.D. andRudo F.G.: Effects of hot plate temperature on the antinociceptive activity of mixed opioid agonistantagonist compounds.Drug Development Res. 7, 277–280, 1986.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • D. Le Bars
    • 1
  1. 1.INSERUM U-161Paris

Personalised recommendations