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. 2011 Feb 2;27(1):61–67. doi: 10.1007/s12264-011-1035-3

Behavioral assessments of the aversive quality of pain in animals

动物痛厌恶情绪的行为学检测

Xu-Jie Zhang 1,2, Tian-Wei Zhang 1,3, San-Jue Hu 1,✉, Hui Xu 1,✉
PMCID: PMC5560275  PMID: 21270905

Abstract

Animals and humans share similar mechanisms of pain detection and similar brain areas involved in pain processing. Also, they show similar pain behaviors, such as reflexed sensation to nociceptive stimuli. Pain is often described in sensory discrimination (algosity) and affective motivation (unpleasantness) dimensions. Both basic and clinical findings indicate that individuals with chronic pain usually suffer more from pain-associated affective disturbances than from the actual pain sensations per se. Although the neural systems responsible for the sensory component of pain have been studied extensively, the neural mechanisms underlying negative affective component are not well understood. This is partly due to the relative paucity of animal paradigms for reliable examination of each component of pain. In humans, the experience of pain and suffering can be reported by language, while in animals, pain can only be inferred through physical and behavioral reactions. Animal behaviors, cognitive psychology and functional brain imaging have made it possible to assess pain affection and pain memory in animals. Animals subjected to either neuropathic injury or inflammatory insult display significant conditioned place aversion to a pain-paired environment in behaviors. The present review aims to summarize the common methods of affective unpleasantness assessment in rats.

Keywords: pain-related negative affect, unpleasantness, conditioned place avoidance, pain

Footnotes

These authors contributed equally to this work.

Contributor Information

San-Jue Hu, Phone: +86-29-84774590, FAX: +86-29-83246270, Email: sjhu@fmmu.edu.cn.

Hui Xu, Phone: +86-29-84774590, FAX: +86-29-83246270, Email: xubz@fmmu.edu.cn.

References

  • [1].Merksey H., Bogduk N. Classification of Chronic Pain. Seattle: IASP Press; 1994. [Google Scholar]
  • [2].Melzack R., Casey K.L. Sensory, motivational and central control determinants of chronic pain: A new conceptual model. In: Kenshalo D.R., editor. The Skin senses. Springfield Illinois: Charles C Thomas; 1968. p. 432. [Google Scholar]
  • [3].Rainville P., Feine J.S., Bushnell M.C., Duncan G.H. A psychophysical comparison of sensory and affective responses to four modalities of experimental pain. Somatosens Mot Res. 1992;9(4):265–277. doi: 10.3109/08990229209144776. [DOI] [PubMed] [Google Scholar]
  • [4].Tracey I., Mantyh P.W. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–391. doi: 10.1016/j.neuron.2007.07.012. [DOI] [PubMed] [Google Scholar]
  • [5].Schnitzler A., Ploner M. Neurophysiology and functional neuroanatomy of pain perception. J Clin Neurophysiol. 2000;17(6):592–603. doi: 10.1097/00004691-200011000-00005. [DOI] [PubMed] [Google Scholar]
  • [6].Vogt B.A. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci. 2005;6(7):533–544. doi: 10.1038/nrn1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].LaBuda C.J., Fuchs P.N. Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation. Neuroscience. 2005;136(1):311–322. doi: 10.1016/j.neuroscience.2005.07.010. [DOI] [PubMed] [Google Scholar]
  • [8].Turk D.C., Rudy T.E. The robustness of an empirically derived taxonomy of chronic pain patients. Pain. 1990;43(1):27–35. doi: 10.1016/0304-3959(90)90047-H. [DOI] [PubMed] [Google Scholar]
  • [9].Johansen J.P., Fields H.L., Manning B.H. The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. Proc Natl Acad Sci U S A. 2001;98(14):8077–8082. doi: 10.1073/pnas.141218998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Treede R.D., Kenshalo D.R., Gracely R.H., Jones A.K. The cortical representation of pain. Pain. 1999;79(2–3):105–111. doi: 10.1016/S0304-3959(98)00184-5. [DOI] [PubMed] [Google Scholar]
  • [11].Sewards T.V., Sewards M. Separate, parallel sensory and hedonic pathways in the mammalian somatosensory system. Brain Res Bull. 2002;58(3):243–260. doi: 10.1016/s0361-9230(02)00783-9. [DOI] [PubMed] [Google Scholar]
  • [12].Tanimoto S., Nakagawa T., Yamauchi Y., Minami M., Satoh M. Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats. Eur J Neurosci. 2003;18(8):2343–2350. doi: 10.1046/j.1460-9568.2003.02952.x. [DOI] [PubMed] [Google Scholar]
  • [13].Deyama S., Nakagawa T., Kaneko S., Uehara T., Minami M. Involvement of the bed nucleus of the stria terminalis in the negative affective component of visceral and somatic pain in rats. Behav Brain Res. 2007;176(2):367–371. doi: 10.1016/j.bbr.2006.10.021. [DOI] [PubMed] [Google Scholar]
  • [14].Gao Y.J., Ren W.H., Zhang Y.Q., Zhao Z.Q. Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats. Pain. 2004;110(1–2):343–353. doi: 10.1016/j.pain.2004.04.030. [DOI] [PubMed] [Google Scholar]
  • [15].Okon E. Factors affecting ultrasound production in infant rodents. J Zoology. 1972;168:139–148. doi: 10.1111/j.1469-7998.1972.tb01344.x. [DOI] [Google Scholar]
  • [16].Hofer M.A., Shair H.N. Isolation distress in two-week-old rats: influence of home cage, social companions, and prior experience with littermates. Dev Psychobiol. 1987;20(4):465–476. doi: 10.1002/dev.420200410. [DOI] [PubMed] [Google Scholar]
  • [17].Ardid D., Jourdan D., Eschalier A., Arabia C., Le Bars D. Vocalization elicited by activation of A delta- and C-fibres in the rat. Neuroreport. 1993;5(2):105–108. doi: 10.1097/00001756-199311180-00002. [DOI] [PubMed] [Google Scholar]
  • [18].Jourdan D., Ardid D., Chapuy E., Eschalier A., Le Bars D. Audible and ultrasonic vocalization elicited by single electrical nociceptive stimuli to the tail in the rat. Pain. 1995;63(2):237–249. doi: 10.1016/0304-3959(95)00049-X. [DOI] [PubMed] [Google Scholar]
  • [19].Calvino B., Besson J., Boehrer A., Depaulis A. Vocalization elicited by activation of A delta- and C-fibres in the rat. Neuroreport. 1996;7(2):581–584. doi: 10.1097/00001756-199601310-00049. [DOI] [PubMed] [Google Scholar]
  • [20].Dinh H.K., Larkin A., Gatlin L., Piepmeier E.J. Rat ultrasound model for measuring pain resulting from intramuscularly injected antimicrobials. PDA J Pharm Sci Technol. 1999;53(1):40–43. [PubMed] [Google Scholar]
  • [21].Han J.S., Bird G.C., Li W., Jones J., Neugebauer V. Computerized analysis of audible and ultrasonic vocalizations of rats as a standardized measure of pain-related behavior. J Neurosci Methods. 2005;141(2):261–269. doi: 10.1016/j.jneumeth.2004.07.005. [DOI] [PubMed] [Google Scholar]
  • [22].Adwanikar H., Ji G., Li W., Doods H., Willis W., Neugebauer V. Spinal CGRP1 receptors contribute to supraspinally organized pain behavior and pain-related sensitization of amygdala neurons. Pain. 2007;132(1–2):53–66. doi: 10.1016/j.pain.2007.01.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Oliveira A.R., Barros H.M. Ultrasonic rat vocalizations during the formalin test: a measure of the affective dimension of pain. Anesth Analg. 2006;102(3):832–839. doi: 10.1213/01.ane.0000196530.72813.d9. [DOI] [PubMed] [Google Scholar]
  • [24].Jourdan D., Ardid D., Eschalier A. Analysis of ultrasonic vocalisation does not allow chronic pain to be evaluated in rats. Pain. 2002;95(1–2):165–173. doi: 10.1016/S0304-3959(01)00394-3. [DOI] [PubMed] [Google Scholar]
  • [25].Williams W.O., Riskin D.K., Mott A.K. Ultrasonic sound as an indicator of acute pain in laboratory mice. J Am Assoc Lab Anim Sci. 2008;47(1):8–10. [PMC free article] [PubMed] [Google Scholar]
  • [26].Kurejova M., Nattenmuller U., Hildebrandt U., Selvaraj D., Stosser S., Kuner R. An improved behavioral assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain. Mol Pain. 2010;6:18. doi: 10.1186/1744-8069-6-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Price D.D. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288(5472):1769–1772. doi: 10.1126/science.288.5472.1769. [DOI] [PubMed] [Google Scholar]
  • [28].Deyama S., Yamamoto J., Machida T., Tanimoto S., Nakagawa T., Kaneko S., et al. Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces paininduced aversion. Neurosci Res. 2007;59(2):199–204. doi: 10.1016/j.neures.2007.06.1473. [DOI] [PubMed] [Google Scholar]
  • [29].Li T.T., Ren W.H., Xiao X., Nan J., Cheng L.Z., Zhang X.H., et al. NMDA NR2A and NR2B receptors in the rostral anterior cingulate cortex contribute to pain-related aversion in male rats. Pain. 2009;146(1–2):183–193. doi: 10.1016/j.pain.2009.07.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Wu L.J., Toyoda H., Zhao M.G., Lee Y.S., Tang J., Ko S.W., et al. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci. 2005;25(48):11107–11116. doi: 10.1523/JNEUROSCI.1678-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Xu H., Wu L.J., Wang H., Zhang X., Vadakkan K.I., Kim S.S., et al. Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci. 2008;28(29):7445–7453. doi: 10.1523/JNEUROSCI.1812-08.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Morimoto M., Morita N., Ozawa H., Yokoyama K., Kawata M. Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain: an immunohistochemical and in situ hybridization study. Neurosci Res. 1996;26(3):235–269. doi: 10.1016/S0168-0102(96)01105-4. [DOI] [PubMed] [Google Scholar]
  • [33].Wang H.C., Wang Y.C., Huang A.C., Chai S.C., Wu Y.S., Wang C.C. Roles of corticosterone in formalin-induced conditioned place aversion in rats. Neurosci Lett. 2009;464(2):122–126. doi: 10.1016/j.neulet.2009.08.053. [DOI] [PubMed] [Google Scholar]
  • [34].Blackburn-Munro G. Pain-like behaviours in animals — how human are they? Trends Pharmacol Sci. 2004;25:299–305. doi: 10.1016/j.tips.2004.04.008. [DOI] [PubMed] [Google Scholar]
  • [35].Hummel M., Lu P., Cummons T.A., Whiteside G.T. The persistence of a long-term negative affective state following the induction of either acute or chronic pain. Pain. 2008;140(3):436–445. doi: 10.1016/j.pain.2008.09.020. [DOI] [PubMed] [Google Scholar]
  • [36].Roth-Isigkeit A., Thyen U., Stoven H., Schwarzenberger J., Schmucker P. Pain among children and adolescents: restrictions in daily living and triggering factors. Pediatrics. 2005;115(2):e152–162. doi: 10.1542/peds.2004-0682. [DOI] [PubMed] [Google Scholar]
  • [37].LaBuda C.J., Fuchs P.N. A behavioral test paradigm to measure the aversive quality of inflammatory and neuropathic pain in rats. Exp Neurol. 2000;163(2):490–494. doi: 10.1006/exnr.2000.7395. [DOI] [PubMed] [Google Scholar]
  • [38].LaBuda C.J., Fuchs P.N. Morphine and gabapentin decrease mechanical hyperalgesia and escape/avoidance behavior in a rat model of neuropathic pain. Neurosci Lett. 2000;290(2):137–140. doi: 10.1016/S0304-3940(00)01340-9. [DOI] [PubMed] [Google Scholar]
  • [39].LaBuda C.J., Fuchs P.N. Low dose aspirin attenuates escape/avoidance behavior, but does not reduce mechanical hyperalgesia in a rodent model of inflammatory pain. Neurosci Lett. 2001;304(3):137–140. doi: 10.1016/S0304-3940(01)01787-6. [DOI] [PubMed] [Google Scholar]
  • [40].Wilson H.D., Boyette-Davis J., Fuchs P.N. The relationship between basal level of anxiety and the affective response to inflammation. Physiol Behav. 2007;90(2–3):506–511. doi: 10.1016/j.physbeh.2006.10.015. [DOI] [PubMed] [Google Scholar]
  • [41].Wilson H.D., Uhelski M.L., Fuchs P.N. Examining the role of the medial thalamus in modulating the affective dimension of pain. Brain Res. 2008;1229:90–99. doi: 10.1016/j.brainres.2008.06.009. [DOI] [PubMed] [Google Scholar]
  • [42].LaGraize S.C., Fuchs P.N. GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate paininduced escape/avoidance behavior. Exp Neurol. 2007;204(1):182–194. doi: 10.1016/j.expneurol.2006.10.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Li T.T., Ren W.H., Xiao X., Nan J., Cheng L.Z., Zhang X.H., et al. NMDA NR2A and NR2B receptors in the rostral anterior cingulate cortex contribute to pain-related aversion in male rats. Pain. 2009;146:183–193. doi: 10.1016/j.pain.2009.07.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Fuchs P.N., Balinsky M., Melzack R. Electrical stimulation of the cingulum bundle and surrounding cortical tissue reduces formalin-test pain in the rat. Brain Res. 1996;743(1–2):116–123. doi: 10.1016/S0006-8993(96)01035-9. [DOI] [PubMed] [Google Scholar]
  • [45].Fuchs P.N., Melzack R. Analgesia induced by morphine microinjection into the lateral hypothalamus of the rat. Exp Neurol. 1995;134(2):277–280. doi: 10.1006/exnr.1995.1058. [DOI] [PubMed] [Google Scholar]

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