Cited by 1,459Pain Mechanisms and TreatmentsAnimal testing and alternativesVeterinary Pharmacology and Anesthesia

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Animal Models of Nociception

Le Bars, Daniel, Gozariu, Manuela, Cadden, Samuel W.·2001·Pharmacological Reviews

DOI 10.1016/s0031-6997(24)01514-x

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Background
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Background
Comparison of analgesic activities of aconitine in different mice pain models
Deng, J., Han, J., Chen, J., Zhang, Y., Huang, Q., Wang, Y., Qi, X., Liu, Z., Leung, E. L., Wang, D., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0249276 · Cited by 57
“Besides, the writhing behavior of mice evoked by acetic acid injection is considered to reflect visceral pain [7, 32], and 0.”
Background
A Novel COX‐2 Inhibitor Pyrazole Derivative Proven Effective as an Anti‐Inflammatory and Analgesic Drug
El‐Din, M. M. M., Senbel, A. M., Bistawros, A., El‐Mallah, A., El‐Din, N. A. N., Bekhit, A. A., & Razik, H. A. A. E. (2010) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2010.00648.x · Cited by 55
Synergism between NSAIDs in the orofacial formalin test in mice
Miranda, H. F., Sierralta, F., & Prieto, J. C. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.12.018 · Cited by 55
Analgesic activity of piracetam: Effect on cytokine production and oxidative stress
Navarro, S. A., Serafim, K. G. G., Mizokami, S. S., Hohmann, M. S., Casagrande, R., & Verri, W. A., Jr. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.02.018 · Cited by 55
GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain
Viguier, F., Michot, B., Kayser, V., Bernard, J., Vela, J. M., Hamon, M., & Bourgoin, S. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.023 · Cited by 59
“Because of the possible occurrence of interferences between the pharmacological effects of drugs and adaptive thermoregulation in the thermal test (Le Bars et al., 2001), we measured skin temperature at the level of hindpaws in rats injected with 5-HT7R agonists or vehicle.”
BackgroundMethod
Animal models of pain
Vierck, C. J. (2006) · Elsevier eBooks · doi:10.1016/b0-443-07287-6/50015-1 · Cited by 56
Antinociceptive and anti-inflammatory effect of Naringenin in different nociceptive and inflammatory mice models
Xue, N., Wu, X., Wu, L., Li, L., & Wang, F. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.11.013 · Cited by 55
“These tests were performed by using thermal, mechanical or electrical stimulus [22].”
Method
Effects of nociceptin/orphanin FQ receptor (NOP) agonist, Ro64-6198, on reactivity to acute pain in mice: Comparison to morphine
Reiss, D. J., Wichmann, J., Tekeshima, H., Kieffer, B. L., & Ouagazzal, A. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.10.031 · Cited by 55
Pereskia aculeata: A plant food with antinociceptive activity
Pinto, N. D. C. C., Duque, A. P. D. N., Pacheco, N. R., Mendes, R. D. F., Motta, E. V. S., Bellozi, P. M. Q., Ribeiro, A. D. D. C., Salvador, M. J., & Scio, E. (2015) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1008144 · Cited by 57
“The mechanisms associated to this response are not totally clear; however, it is recognized that this test is effective only to determine the analgesic activity of opioid agonists (Le Bars et al., 2001).”
Background
Somatosensory evoked potentials in the telencephalon of Atlantic salmon (Salmo salar) following galvanic stimulation of the tail
Nordgreen, J., Horsberg, T. E., Ranheim, B., & Chen, A. C. N. (2007) · Journal of Comparative Physiology A · doi:10.1007/s00359-007-0283-1 · Cited by 54
“However, a drawback is that it activates all peripheral Wbres including the large-diameter A-Wbres ( Le Bars et al. 2001 ).”
Background
Antinociceptive activity of Buddleja globosa (matico) in several models of pain
Backhouse, N., Delporte, C. L., Apablaza, C., Farías, M., Goïty, L., Arrau, S., Negrete, R. E., Castro, C., & Miranda, H. F. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.06.022 · Cited by 54
Antiinflammatory and antinociceptive activities of Blechnum occidentale L. extract
Nonato, F. R., Barros, T. A. A., Angélica, M., Oliveira, C. E. C., dos Santos, R. R., Soares, M. B. P., & Villarreal, C. F. (2009) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2009.06.005 · Cited by 54
Antinociceptive and anti-inflammatory effects of Memora nodosa and allantoin in mice
Florentino, I. F., da Silva, D. P. B., Galdino, P. M., Lino, R. C., Martins, J. L. R., Silva, D. M., de Paula, J. R., Tresvenzol, L. M. F., & Costa, É. A. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.04.010 · Cited by 54
Antinociceptive and anti-inflammatory effects of the aerial parts ofArtemisia dracunculusin mice
Eidi, A., Oryan, S., Zaringhalam, J., & Jahangiri-rad, M. (2015) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1056312 · Cited by 53
“Phase I results from direct stimulation of nociceptors, while phase II involves a period of sensitization, during which inflammatory phenomena occur through peripheral mechanisms (Le Bars et al., 2001).”
Background
5-HT1A receptors in endogenous regulation of neuropathic hypersensitivity in the rat
Wei, H., & Pertovaara, A. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.02.019 · Cited by 53
Carvacryl acetate, a derivative of carvacrol, reduces nociceptive and inflammatory response in mice
Damasceno, S., Oliveira, F. R. A. M., Carvalho, N. S., Brito, C. F., Silva, I. S., Sousa, F. B. M., Silva, R. O., de Sousa, D. P., Barbosa, A. L. D. R., de Freitas, R. M., et al. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.11.001 · Cited by 53
Antinociceptive activity of the essential oil from Artemisia ludoviciana
Anaya‐Eugenio, G. D., Rivero‐Cruz, I., Bye, R. A., Linares, E., & Mata, R. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.01.008 · Cited by 53
Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice
Masocha, W., Kombian, S. B., & Edafiogho, I. O. (2016) · Scientific Reports · doi:10.1038/srep21582 · Cited by 53
Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives
Domiati, S. A., El‐Mallah, A., Ghoneim, A. I., Bekhit, A. A., & Razik, H. A. A. E. (2016) · Inflammopharmacology · doi:10.1007/s10787-016-0270-7 · Cited by 53
Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities
da Fonsêca, D. V., Salgado, P. R. R., Neto, H. D. C. A., Golzio, A. M. F. D. O., Filho, M. R. D. C., de Melo, C. G. F., Leite, F. C., Piuvezam, M. R., Pordeus, L. C. D. M., Barbosa‐Filho, J. M., et al. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.06.005 · Cited by 53
Looking beyond the intervertebral disc: the need for behavioral assays in models of discogenic pain
Mosley, G. E., Evashwick‐Rogler, T. W., Lai, A., & Iatridis, J. C. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13429 · Cited by 53
Age and Sex Differences in Acute and Osteoarthritis-Like Pain Responses in Rats
Ro, J. Y., Zhang, Y., Tricou, C., Yang, D., Silva, J. T. D., & Zhang, R. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz186 · Cited by 52
“Immobility, while not often recorded as an indicator of pain, is recognized as a nocifensive behavior, especially during intense pain (29,30).”
Background
Estimation of antinociceptive and anti-inflammatory activity on Geranium pratense subsp. finitimum and its phenolic compounds
Küpeli̇, E., Tatlı, I. İ., Akdemir, Z. Ş., & Yeşilada, E. (2007) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2007.08.005 · Cited by 53
Ultrasonic Rat Vocalizations During the Formalin Test: A Measure of the Affective Dimension of Pain?
de Oliveira, A. R., & Barros, H. M. T. (2006) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000196530.72813.d9 · Cited by 53
Synthesis of new 1-phenyl-3-{4-[(2E)-3-phenylprop-2-enoyl]phenyl}-thiourea and urea derivatives with anti-nociceptive activity
dos Santos, L., Lima, L. A., Filho, V. C., Corrêa, R., Buzzi, F. D. C., & Nunes, R. J. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.08.019 · Cited by 53
Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis
Liu, X., & Guo, S. (2011) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2011.01655.x · Cited by 52
The flavonoid 6-methoxyflavone allays cisplatin-induced neuropathic allodynia and hypoalgesia
Shahid, M. M., Subhan, F., Ahmad, N., & Sewell, R. D. E. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.09.108 · Cited by 52
“These paradigms are suitable for assessing both tonic visceral nociception and centrally mediated acute phasic nociception, respectively [21, 28-30].”
Fan-Shaped Body Neurons in the Drosophila Brain Regulate Both Innate and Conditioned Nociceptive Avoidance
Hu, W., Peng, Y., Sun, J., Zhang, F., Zhang, X., Wang, L., Li, Q., & Zhong, Y. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.028 · Cited by 52
Pharmacokinetic/Pharmacodynamic Modeling of the Antinociceptive Effects of (+)-Tramadol in the Rat: Role of Cytochrome P450 2D Activity
Garrido, M. J., Sayar, O., Segura, C., Rapado, J., Dios-Viéitez, M. D. C., Renedo, M. J., & Trocóniz, I. F. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.047779 · Cited by 52
“T and ( )-M1 is still missing and would require a more appropriate animal model for antinociception to explore the nonopioid component in the response (Le Bars et al., 2001).”
Background
Effect of crocin on the morphine‐induced antinociception in the formalin test in rats
Tamaddonfard, E., & Hamzeh‐Gooshchi, N. (2009) · Phytotherapy Research · doi:10.1002/ptr.2965 · Cited by 51
“Many nociceptive tests in animals have been developed to study the mechanisms of pain and analgesia (Le Bars et al., 2001).”
Background
Opioid modulation of reflex versus operant responses following stress in the rat
King, C. D., Devine, D. P., Vierck, C. J., Mauderli, A. P., & Yezierski, R. P. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.04.012 · Cited by 51
The Ubiquitin Ligase MYCBP2 Regulates Transient Receptor Potential Vanilloid Receptor 1 (TRPV1) Internalization through Inhibition of p38 MAPK Signaling
Holland, S. M., Coste, O., Zhang, D. D., Pierre, S. C., Geißlinger, G., & Scholich, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.154765 · Cited by 53
Morphine uptake, disposition, and analgesic efficacy in the common goldfish (Carassius auratus)
Newby, N. C., Wilkie, M. P., & Stevens, D. (2009) · Canadian Journal of Zoology · doi:10.1139/z09-023 · Cited by 51
The Antinociceptive Effects of AR-A014418, a Selective Inhibitor of Glycogen Synthase Kinase-3 Beta, in Mice
Martins, D. F., Rosa, A. O., Gadotti, V. M., Mazzardo‐Martins, L., do Nascimento, F. P., Egea, J., López, M. G., & Santos, A. R. S. (2010) · Journal of Pain · doi:10.1016/j.jpain.2010.06.007 · Cited by 51
Investigation of the Anti-Inflammatory and Analgesic Activities of Ethanol Extract of Stem Bark of SonapathaOroxylum indicum In Vivo
Lalrinzuali, K., Vabeiryureilai, M., & Jagetia, G. C. (2016) · International Journal of Inflammation · doi:10.1155/2016/8247014 · Cited by 55
“The inflammatory phase induced pain evokes a combination of stimuli, including inflammation of peripheral tissues and mechanisms of central sensitization [50, 51].”
Background
Influence of a low dose of silver nanoparticles on cerebral myelin and behavior of adult rats
Dąbrowska‐Bouta, B., Zięba, M., Orzelska‐Górka, J., Skalska, J., Sułkowski, G., Frontczak‐Baniewicz, M., Talarek, S., Listos, J., & Strużyńska, L. (2016) · Toxicology · doi:10.1016/j.tox.2016.07.007 · Cited by 51
A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats
Shahid, M. M., Subhan, F., Ahmad, N., & Ullah, I. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1807-z · Cited by 55
The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model
Stepanović-Petrović, R. M., Tomic´, M. A., Vuckovic, S. M., Paranos, S. L., Ugrešić, N. D., Prostran, M. S., Milovanović, S. R., & Bošković, B. (2008) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e318172b993 · Cited by 51
“Writhing Test This test was selected as a model of acute peritoneovisceral pain, which could be a model of clinically relevant intestinal pain in humans.(4,23,24) Mice were injected i.”
Method
Impaired Pain Sensation in Mice Lacking Prokineticin 2
Hu, W., Zhang, C., Li, J., Luo, Z. D., Amadesi, S., Bunnett, N. W., & Zhou, Q. (2006) · Molecular Pain · doi:10.1186/1744-8069-2-35 · Cited by 51
Dexketoprofen-induced antinociception in animal models of acute pain: Synergy with morphine and paracetamol
Miranda, H. F., Puig, M. M., Dürsteler, C., Prieto, J. C., & Pinardi, G. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.025 · Cited by 51
Antihyperalgesic effects of imidazoline I 2receptor ligands in rat models of inflammatory and neuropathic pain
Li, J., Thorn, D. A., Qiu, Y., Peng, B., & Zhang, Y. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12555 · Cited by 50
“Writhing test is often used to model chemical irritant provoked visceral pain (Le Bars et al., 2001) and the neurobiology of visceral pain is different from inflammatory pain, which CFA treatment is designed to model (Almarestani et al., 2011; Gebhart and Bielefeldt, 2011).”
Analgesic effects of the somatostatin sst4 receptor selective agonist J-2156 in acute and chronic pain models
Sándor, K., Elekes, K., Szabó, Á., Pintér, E., Engström, M., Wurster, S., Szolcsányi, J., & Helyes, Z. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.03.082 · Cited by 50
Lectin extracted from Canavalia grandiflora seeds presents potential anti-inflammatory and analgesic effects
Nunes, B. S., Rensonnet, N. S., Dal-Secco, D., Vieira, S. M., Cavada, B. S., Teixeira, E. H., de Moura, T. R., Teixeira, C. S., Clemente‐Napimoga, J. T., Cunha, F. Q., et al. (2009) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-009-0397-9 · Cited by 49
“3d), which involves a period of sensitization during which inflammatory phenomena occur (Le Bars et al. 2001).”
Background
Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs
Pieper, K., Schuster, T., Levionnois, O., MATIS, U., & Bergadano, A. (2010) · The Veterinary Journal · doi:10.1016/j.tvjl.2010.01.013 · Cited by 49
Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses
Nobre, M. E. P., Correia, A. O., Borges, M. D. B., Sampaio, T. M. A., Chakraborty, S. A., Gonçalves, D. D. O., Brito, G. A. D. C., Leal, L. K. A. M., Felipe, C. F. B., Lucetti, D. L., et al. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.02.011 · Cited by 49
“Although COX-2 inhibitors present less upper gastrointestinal toxicity than traditional NSAIDs, both selective and nonselective COX inhibitors (excluding aspirin) can exert deleterious effects on the cardiovascular system [5,6].”
BackgroundInfluential
Specific activation of the paralemniscal pathway during nociception
Frangeul, L., Porrero, C., García‐Amado, M., Maimone, B., Maniglier, M., Clascá, F., & Jabaudon, D. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12524 · Cited by 49
“For this purpose, we unilaterally microinjected capsaicin, an algogenic chemical that activates TRPV1 receptors on nerve terminals (Le Bars et al., 2001; Noma et al., 2008), into the whisker pad.”
Antinociceptive Activity of Methanol Extract ofMuntingia calaburaLeaves and the Mechanisms of Action Involved
Sani, M. H. M., Zakaria, Z. A., Balan, T., Teh, L. K., & Salleh, M. Z. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/890361 · Cited by 49
The effects of age and sex on pain sensitivity in young lambs
Guesgen, M. J., Beausoleil, N. J., Minot, E. O., Stewart, M., Jones, G., & Stafford, K. J. (2011) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2011.09.008 · Cited by 49
Vocal communication of simulated pain
Raine, J., Pisanski, K., Simner, J., & Reby, D. (2018) · Bioacoustics · doi:10.1080/09524622.2018.1463295 · Cited by 49
“Kenner 1993; Fuller et al. 1993) and many nonhuman mammals ( Dubner et al. 1994; Bars et al. 2001; Bufalari et al. 2007; Mogil 2009) produce pain vocalisations in response to noxious stimuli, that are in turn detected and processed via similar mechanisms in humans and nonhuman mammals (Schnitzler…”
Nociceptive activation in spinal cord and brain persists during deep general anaesthesia
Lichtner, G., Auksztulewicz, R., Velten, H., Mavrodis, D., Scheel, M., Blankenburg, F., & von Dincklage, F. (2018) · British Journal of Anaesthesia · doi:10.1016/j.bja.2018.03.031 · Cited by 49
Anti-nociceptive and anti-inflammatory activities of crude root extract and solvent fractions of Cucumis ficifolius in mice model
Demsie, D. G., Yimer, E. M., Berhe, A. H., Altaye, B. M., & Berhe, D. F. (2019) · Journal of Pain Research · doi:10.2147/jpr.s193029 · Cited by 49
“The two responses are supraspinally integrated, and sensitive to opioid analgesics.(38,40) The plate was maintained at 55oC, and at this temperature only opioid-like agents are active.”
Background
Heterocycles 48. Synthesis, Characterization and Biological Evaluation of Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives as Anti-Inflammatory Agents
Cristina, A., Leonte, D., Vlase, L., Bencze, L., Imre, S., Marc, G., Apan, B., Mogoșan, C., & Zaharia, V. (2018) · Molecules · doi:10.3390/molecules23102425 · Cited by 37
“The nociceptive withdrawal threshold was assessed by Randall-Selitto test [30,46].”
Optimization of static magnetic field parameters improves analgesic effect in mice
László, J., Reiczigel, J., Székely, L., Gasparics, A., Bogár, I., Bors, L., Rácz, B., & Gyires, K. (2007) · Bioelectromagnetics · doi:10.1002/bem.20341 · Cited by 48
Antinociceptive and neuropharmacological activities of methanol extract of Phoenix sylvestris fruit pulp
Shajib, M. S., Akter, S., Ahmed, T., & Imam, M. Z. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00212 · Cited by 48
Leishmania infection: painful or painless?
Borghi, S. M., Fattori, V., Costa, I. C., Pinge‐Filho, P., Pavanelli, W. R., & Verri, W. A., Jr. (2016) · Parasitology Research · doi:10.1007/s00436-016-5340-7 · Cited by 48
“…hyperalgesia utilizes other methods, such as through cold stimulus, von Frey filaments , electronic pressure meter, or Randall & Selitto tests, given that these tests investigate different aspects of physiological changes associated with nociceptive signals (Cunha et al. 2004; Le Bars et al. 2001).”
Method

Authors: Le Bars, D., Gozariu, M., & Cadden, S. W.
Venue: Pharmacological Reviews
Publisher: Elsevier BV
Published: 2001-12
Volume: 53
Issue: 4
Pages: 597-652
ISSN: 0031-6997 (ISSN-L)
DOI: 10.1016/s0031-6997(24)01514-x
OpenAlex: W4406058850
Cited by: 1,459
References: 621
Citations by year: 2026: 39 · 2025: 31 · 2024: 22 · 2023: 34 · 2022: 42 · 2021: 52 · 2020: 42 · 2019: 38 · 2018: 64 · 2017: 98 · 2016: 107 · 2015: 121 · 2014: 117 · 2013: 86 · 2012: 87
FWCI: 4.39
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacological Reviews (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
Keywords: animal models of pain, nociception, animal pain assessment, nociceptive stimuli, thermal pain, mechanical pain, chemical pain, electrical pain, nociceptive threshold, spinal reflexes, inflammation, homeostatic mechanisms
MeSH terms: Analgesics, Animals, Disease Models, Animal, Humans, Nerve Fibers, Pain, Pain Measurement

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