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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Ethical guidelines for investigations of experimental pain in conscious animals.
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A METHOD FOR DETERMINING LOSS OF PAIN SENSATION
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An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat
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The formalin test in mice: dissociation between inflammatory and non-inflammatory pain
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ACETIC ACID FOR ANALGESIC SCREENING
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Background
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Background
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Background
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Method
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Background
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BackgroundInfluential
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Sucrose-induced analgesia during early life modulates adulthood learning and memory formation
Nuseir, K. Q., Alzoubi, K. H., Alabwaini, J., Khabour, O. F., & Kassab, M. I. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.04.002 · Cited by 33
Optimal interval for hot water immersion tail-flick test in rats
Zhou, Q., Bao, Y., Zhang, X., Zeng, L., Wang, L., Wang, J., & Jiang, W. (2013) · Acta Neuropsychiatrica · doi:10.1017/neu.2013.57 · Cited by 33
“Moreover, the rate at which tail temperature increases is different from that of the radiant heat test, in which the rate is approximately the square root of the time required to provoke a tail-flick response in the rat; this is relatively slow compared with the more or less linear rate of increase in the hot water im…”
Background
Impact of Physical Activity on Pain Perception in an Animal Model of Endometriosis
Hernández, S., Cruz, M. L., Torres-Reverón, A., & Appleyard, C. B. (2015) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.5000231 · Cited by 33
“Hyperalgesia was tested on a hot plate measuring the response threshold to thermal stimuli (23).”
Background
Sensory neuropathy and nociception in rodent models of Parkinson's disease
Valek, L., Auburger, G. W. J., & Tegeder, I. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039396 · Cited by 33
Antinociceptive and Anti-Inflammatory Activities of Crude Methanolic Extract of Red Alga Bryothamnion triquetrum
Silva, L. H. A. C., da Matta, C. B. B., de Araújo, M. V., Barbosa‐Filho, J. M., de Lira, D. P., Santos, B. V. D. O., de Miranda, G. E. C., & Alexandre‐Moreira, M. S. (2012) · Marine Drugs · doi:10.3390/md10091977 · Cited by 33
“stimulus induces two kinds of behavior: paw licking and jumping [58,59].”
Background
Interaction of Morphine With a New α2-Adrenoceptor Agonist in Mice
Sudo, R. T., Calasans-Maia, J. A., Galdino, S. L., de Lima, M. D. C. A., Zapata‐Sudo, G., Hernandes, M. Z., & Pitta, I. D. R. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.08.001 · Cited by 33
Involvement of 5-HT2 serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome
de Oliveira, R. C., de Oliveira, R., Ferreira, C. M. D. R., & Coimbra, N. C. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.03.033 · Cited by 33
Anti-allodynic Effects of Obtusifolin and Gluco-Obtusifolin against Inflammatory and Neuropathic Pain
He, Z., Wei, W., Li, S., Ling, Q., Liao, K., & Wang, X. (2014) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.c14-00307 · Cited by 33
The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy
Gabra, B. H., Berthiaume, N., Sirois, P., Nantel, F., & Battistini, B. J. (2006) · Biological Chemistry · doi:10.1515/bc.2006.018 · Cited by 33
Shape-memory collagen scaffold combined with hyaluronic acid for repairing intervertebral disc
Koo, Y. W., Lim, C. S., Darai, A., Lee, J., Kim, W.-J., Han, I., & Kim, G. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00368-9 · Cited by 32
“The major observations of this study with regard to the effects exerted by the hydrogels are as follows: (1) alleviation of mechanical allodynia in a rat tail nucleotomy model [67]; (2) restoration of the disc anatomy and water content of IVDs; (3) preservation of the PG content and disc structure; (4) restoration of…”
Background
Effects of the triple monoamine uptake inhibitor amitifadine on pain-related depression of behavior and mesolimbic dopamine release in rats
Miller, L. L., Leitl, M. D., Banks, M. L., Blough, B. E., & Negus, S. S. (2015) · Pain · doi:10.1016/j.pain.0000000000000018 · Cited by 32
“relevant chemical noxious stimulus for preclinical studies of pain and analgesia in rodents.(9,15,23,33) In rats, IP acid depresses extracellular DA levels in nucleus accumbens (NAc) and also depresses intracranial self-stimulation (ICSS), an operant behavior”
Background
α5GABAAReceptors Mediate Tonic Inhibition in the Spinal Cord Dorsal Horn and Contribute to the Resolution Of Hyperalgesia
Pérez-Sánchez, J., Lorenzo, L.-É., Lecker, I., Zurek, A. A., Labrakakis, C., Bridgwater, E. M., Orser, B. A., Koninck, Y. D., & Bonin, R. P. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23981 · Cited by 32
Urinary metabolomics study on the anti-inflammation effects of flavonoids obtained from Glycyrrhiza
Wei, M., Ma, Y., Liu, Y., Zhou, Y., Men, L., Yue, K., Pi, Z., Liu, Z., & Liu, Z. (2018) · Journal of Chromatography B · doi:10.1016/j.jchromb.2018.04.007 · Cited by 32
Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies
Μaione, F., Minosi, P., Giannuario, A. D., Raucci, F., Chini, M. G., Vita, S. D., Bifulco, G., Mascolo, N., & Pieretti, S. (2019) · Molecules · doi:10.3390/molecules24132453 · Cited by 32
“To better investigate its analgesic profile, we finally tested the AG pharmacological profile in an acetic acid-induced writhing test, a commonly used method for monitoring preliminary antinociceptive activity, since in this test both central and peripheral analgesics are detected [53].”
BackgroundMethodInfluential
Biosynthesis of copperoxide nanoparticles using Abies spectabilis plant extract and analyzing its antinociceptive and anti-inflammatory potency in various mice models
Liu, H., Zheng, S., Xiong, H., Alwahibi, M. S., & Niu, X. (2020) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2020.07.006 · Cited by 32
Chapter 24 Referred pain from internal organs
Giamberardino, M. A., Affaitati, G., & Costantini, R. (2006) · Handbook of clinical neurology · doi:10.1016/s0072-9752(06)80028-x · Cited by 32
Polysaccharides isolated from Digenea simplex inhibit inflammatory and nociceptive responses
Pereira, J. G., Mesquita, J. X., Aragão, K. S., Franco, Á. X., de Souza, M. H. L. P., de Brito, T. V., Dias, J. M., Silva, R. O., Medeiros, J. V. R., de Oliveira, J. S., et al. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.01.105 · Cited by 32
Extraction optimization and antinociceptive activity of (1⟶3)-β-d-glucan from Rhodotorula mucilaginosa
Valasques, G. L., de Lima, F. O., Boffo, E. F., Santos, J. D. G., da Silva, B. C., & de Assis, S. A. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.01.064 · Cited by 32
The Study of Analgesic Effects ofLeonurus cardiacaL. in Mice by Formalin, Tail Flick and Hot Plate Tests
Rezaee-Asl, M., Sabour, M., Nikoui, V., Ostadhadi, S., & Bakhtiarian, A. (2014) · International Scholarly Research Notices · doi:10.1155/2014/687697 · Cited by 32
“direct formalin stimulation of the sensorial C-fibers followed by substance P release [24], and the second phase (inflammatory) principally due to a following inflammation reaction in the peripheral tissue mediated by the release of various inflammatorymediators has been relatedwith the augmented level of PG, stimulat…”
Background
Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending serotonergic modulation in inflammatory pain induced in formalin and carrageenan rat models
Yang, J. H., Bae, H., Ki, H. G., Oh, J. M., Kim, W. M., Lee, H. G., Yoon, M. H., & Choi, J. I. (2013) · British Journal of Anaesthesia · doi:10.1093/bja/aet336 · Cited by 32
Antinociceptive effects of (O-methyl)-N-benzoyl tyramine (riparin I) from Aniba riparia (Nees) Mez (Lauraceae) in mice
de Araújo, F. L. O., de Melo, C. T. V., Rocha, N. F. M., Moura, B. A. R., Leite, C. P., do Amaral, J. F., Barbosa‐Filho, J. M., Gutierrez, S. J. C., Vasconcelos, S. M. M., Viana, G. S. B., et al. (2009) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-009-0433-9 · Cited by 32
Sensitivity of quantitative sensory models to morphine analgesia in humans
Olesen, A. E., Brock, C., Sverrisdóttir, E., Larsen, I. M., & Drewes, A. M. (2014) · Journal of Pain Research · doi:10.2147/jpr.s73044 · Cited by 31
“Electrical pain is phasic, and intense electrical stimuli excites all peripheral fibers in a nondifferential fashion.(8) Thus, analgesic effects of opioids on this dynamic endpoint have previously only been demonstrated in patients with chronic pain, suggesting that an upregulated pain system is needed for demonstrati…”
How Can Animal Models Inform on the Transition to Chronic Symptoms in Whiplash?
Winkelstein, B. A. (2011) · Spine · doi:10.1097/brs.0b013e3182387f96 · Cited by 34
Influence of Clonidine and Ketamine on m-RNA Expression in a Model of Opioid-Induced Hyperalgesia in Mice
Ohnesorge, H., Feng, Z., Zitta, K., Steinfath, M., Albrecht, M., & Bein, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079567 · Cited by 31
“This paradigm was used because the reaction on non noxious mechanical stimulation is influenced not only by spinal but also in a greater extend by supraspinal mechanisms [16].”
Method
Polydeoxyribonucleotide Ameliorates Inflammation and Apoptosis in Achilles Tendon-Injury Rats
Rho, J. H., Ko, I., Jin, J., Hwang, L., Kim, S., Chung, J.-Y., Hwang, T.-J., & Han, J. (2020) · International Neurourology Journal · doi:10.5213/inj.2040428.214 · Cited by 31
“The planta test was performed for the determination of thermal hyperalgesia 16 days after injury to the Achilles tendon, like the method described below [18].”
Method
Musculoskeletal Sensitization and Sleep: Chronic Muscle Pain Fragments Sleep of Mice without Altering Its Duration
Sutton, B. C., & Opp, M. R. (2014) · SLEEP · doi:10.5665/sleep.3486 · Cited by 35
Antinociceptive and anti-inflammatory effects of myricetin 3-O-β-galactoside isolated from Davilla elliptica: involvement of the nitrergic system
Azevedo, A. D. O., Campos, J. J., Galdino, G. S., Veloso, C. C., Duarte, I. D. G., Braga, F. C., & Perez, A. C. (2015) · Journal of Natural Medicines · doi:10.1007/s11418-015-0913-9 · Cited by 31
“drugs [40].”
Differential Development of Antinociceptive Tolerance to Morphine and Fentanyl Is Not Linked to Efficacy in the Ventrolateral Periaqueductal Gray of the Rat
Bobeck, E. N., Haseman, R. A., Hong, D., Ingram, S., & Morgan, M. M. (2012) · Journal of Pain · doi:10.1016/j.jpain.2012.05.005 · Cited by 31
Anti-inflammatory and analgesic effects of 6α,7β–dihydroxy-vouacapan-17β-oic acid isolated from Pterodon emarginatus Vog. fruits
Galceran, C. B., Sertié, J. A. A., Lima, C. S., & Carvalho, J. C. T. (2011) · Inflammopharmacology · doi:10.1007/s10787-011-0081-9 · Cited by 30
“Furthermore, blocking the first phase with the subcutaneous administration of lidocaine does not suppress second-phase responses ( Le Bars et al. 2001; Dalles et al. 1995; Taylor et al. 1995, 1997).”
Background
Peripheral and Central Determinants of a Nociceptive Reaction: An Approach to Psychophysics in the Rat
Benoist, J. M., Pincedé, I., Ballantyne, K., Plaghki, L., & Bars, D. L. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003125 · Cited by 30
“045uC(2)/s in order to achieve the 2–4 seconds range, shown as a yellow area, for the TFL commonly reported in the literature for the classical tail-flick test in control situations [35].”
BackgroundInfluential
The dose–response relation for the antinociceptive effect of morphine in a fish, rainbow trout
JONES, S. G., Kamunde, C., LEMKE, K., & STEVENS, E. D. (2012) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2011.01363.x · Cited by 30
“Electrical stimuli have been used as a noxious stimulus in a variety of mammals, and their advantages and disadvantages have been reviewed (Le Bars et al., 2001).”
BackgroundMethod
Animal models for central poststroke pain: a critical comprehensive review
Vloo, P. D., Morlion, B. J., van Loon, J., & Nuttin, B. (2016) · Pain · doi:10.1097/j.pain.0000000000000722 · Cited by 30
“Evidently, every test has its advantages and disadvantages.(4,26,53,64) Nevertheless, there are 3 important remarks to be made regarding the use of the aforementioned tests.”
Background
Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis
Hernández, S., Cruz, M. L., Seguinot, I., Torres-Reverón, A., & Appleyard, C. B. (2017) · Reproductive Sciences · doi:10.1177/1933719116687655 · Cited by 31
Comparative effects of the ω3 polyunsaturated fatty acid derivatives resolvins E1 and D1 and protectin DX in models of inflammation and pain
Fonseca, F. C. D. S., Orlando, R. M., Turchetti-Maia, R. M. M., & Francischi, J. N. (2017) · Journal of Inflammation Research · doi:10.2147/jir.s142424 · Cited by 30
“11 It is conceivable that similar mechanisms account for the results observed for both Rvs, but species differences cannot be overlooked, 33 especially considering that rat paw edema in response to CG offers the best translational responses in humans.”
Mechanical nociceptive thresholds using four probe configurations in horses
Taylor, P. M., Crosignani, N., Lopes, C., da Rosa, A. C., Luna, S. P. L., & Filho, J. N. P. P. (2015) · Veterinary Anaesthesia and Analgesia · doi:10.1111/vaa.12274 · Cited by 30
Effect of Subpressor Dose of Angiotensin II on Pain-Related Behavior in Relation with Neuronal Injury and Activation of Satellite Glial Cells in the Rat Dorsal Root Ganglia
Pavel, J., Oroszova, Z., Hricová, Ľ., & Lukáčová, N. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-9934-7 · Cited by 30
Antinociceptive, genotoxic and histopathological study of Heliopsis longipes S.F. Blake in mice
Cariño‐Cortés, R., Gayosso-De-Lucio, J. A., Ortiz, M. I., Sánchez‐Gutiérrez, M., García-Reyna, P., Cilia-López, V. G., Pérez‐Hernández, N., Moreno, E., & Ponce-Monter, H. A. (2010) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2010.04.037 · Cited by 30
Granulocyte-Colony Stimulating Factor (G-CSF) induces mechanical hyperalgesia via spinal activation of MAP kinases and PI3K in mice
de Carvalho, T. T., Flauzino, T., Otaguiri, E. S., Batistela, A. P., Zarpelon, A. C., Cunha, T. M., Ferreira, S. H., Cunha, F. Q., & Verri, W. A., Jr. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.12.027 · Cited by 30
Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity
Fernández, A. P., Serrano, J., Martínez‐Murillo, R., & Martı́nez, A. (2010) · Endocrinology · doi:10.1210/en.2010-0121 · Cited by 30
“the tail-flick latency and the paw withdrawal latency tests, both of which basically measure spinal reflexes (20, 21).”
Background
Heat injury-induced drop of the noxious heat threshold measured with an increasing-temperature water bath: A novel rat thermal hyperalgesia model
Bölcskei, K., Horváth, D., Szolcsányi, J., & Pethö, G. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.01.097 · Cited by 30
Analgesic effects of rosemary essential oil and its interactions with codeine and paracetamol in mice.
Rašković, A., Milanović, I., Pavlović, N., Milijašević, B., Ubavic, M., & Mikov, M. (2015) · PubMed · Cited by 30
Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses
Luna, S. P. L., Lopes, C., da Rosa, A. C., Oliveira, F. A., Crosignani, N., Taylor, P. M., & Pantoja, J. C. F. (2014) · Equine Veterinary Journal · doi:10.1111/evj.12332 · Cited by 30
Antinociception Induced by Chronic Glucocorticoid Treatment is Correlated to Local Modulation of Spinal Neurotransmitter Content
Pinto‐Ribeiro, F., Moreira, V., Pêgo, J. M., Leão, P., Almeida, A., & Sousa, N. (2009) · Molecular Pain · doi:10.1186/1744-8069-5-41 · Cited by 30
“In contrast, the HP test involves a supraspinally integrated response, and thus, represents a more complex behavioural response [36].”
Background
Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord
Xu, Y. X. Z., Liu, J., He, M., Liu, R., Belegu, V., Dai, P., Liu, W., Wang, W., Xia, Q., Shang, F., et al. (2016) · Scientific Reports · doi:10.1038/srep27512 · Cited by 30
Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models
Gehrcke, M., Sari, M. H. M., Ferreira, L. M., Barbieri, A. V., Giuliani, L. M., Prado, V. C., Nadal, J. M., Farago, P. V., Nogueira, C. W., & Cruz, L. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.09.050 · Cited by 30
Dopamine D4receptor stimulation prevents nigrostriatal dopamine pathway activation by morphine: relevance for drug addiction
Rivera, A., Gago, B., Suárez‐Boomgaard, D., Yoshitake, T., Roales‐Buján, R., Valderrama‐Carvajal, A., Bilbao, A., Medina-Luque, J., Dı́az-Cabiale, Z., Craenenbroeck, K. V., et al. (2016) · Addiction Biology · doi:10.1111/adb.12407 · Cited by 31
Central and Peripheral Mechanisms in ApoE4-Driven Diabetic Pathology
Koren-Iton, A., Salomon‐Zimri, S., Smolar, A., Stein, E. S., Dori, A., Chapman, J., & Michaelson, D. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041289 · Cited by 28
“Pain sensitivity (nociception) was assessed using the hot plate test [74].”
Role of Descending Serotonergic Fibers in the Development of Pathophysiology after Spinal Cord Injury (SCI): Contribution to Chronic Pain, Spasticity, and Autonomic Dysreflexia
Fauss, G. N. K., Hudson, K. E., & Grau, J. W. (2022) · Biology · doi:10.3390/biology11020234 · Cited by 29
Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris.
Taherian, A. A., Babaei, M., Vafaei, A. A., Jarrahi, M., Jadidi, M., & Sadeghi, H. M. M. (2009) · PubMed · Cited by 29
Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents
Taïwé, G. S., Bum, E. N., Talla, E., Dimo, T., Sidiki, N., Dawé, A., Nguimbou, R. M., Dzeufiet, P. D. D., & WAARD, M. M. D. (2012) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2012.02.024 · Cited by 29
Nitric oxide/cGMP pathway mediates orofacial antinociception induced by electroacupuncture at the St36 acupoint
Almeida, R. T., & Duarte, I. D. G. (2007) · Brain Research · doi:10.1016/j.brainres.2007.10.060 · Cited by 29
Systemic amitriptyline administration does not prevent the increased thermal response induced by paradoxical sleep deprivation
Damasceno, F., Skinner, G. O., Gomes, A., Araújo, P. C. O., & Almeida, O. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.07.005 · Cited by 29
“Although the neural basis of the observed reactions in these tests is poorly understood, the formalin and mechanical test responses have been considered to be complex behaviors and the rat tail withdrawal and acetic acid test responses to be spinal reflexes (for review, see Le Bars et al., 2001).”
Electroencephalographic Changes Associated with Antinociceptive Actions of Lidocaine, Ketamine, Meloxicam, and Morphine Administration in Minimally Anaesthetized Dogs
Kaka, U., Chen, H. C., Meng, G. Y., Fakurazi, S., Kaka, A., Behan, A. A., & Ebrahimi, M. M. (2015) · BioMed Research International · doi:10.1155/2015/305367 · Cited by 29

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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