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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Oliveira, P. D. A., de Almeida, T. B., de Oliveira, R. G., Gonçalves, G. M., de Oliveira, J. M., Santos, B. B. N., Laureano‐Melo, R., Côrtes, W. D. S., França, T. N., Vasconcellos, M. L. A. A., et al. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.07.022 · Cited by 17
ANTI-INFLAMMATORY, ANALGESIC AND ANTI - PYRETIC ACTIVITY OF CASSAVA LEAVES EXTRACT
Okechukwu, P. N., Bokanisereme, & Umar, F. Y. (2013) · Asian Journal of Pharmaceutical and Clinical Research · Cited by 17
Nociceptive and inflammatory responses induced by formalin in the orofacial region of rats: Effect of anti-TNFα strategies
Pereira, P. J. S., Dornelles, F. N., Santos, D. S., Calixto, J. Β., Morrone, F. B., & Campos, M. M. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.10.001 · Cited by 17
Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway
Zakaria, Z. A., Roosli, R. A. J., Marmaya, N. H., Omar, M. H., Basir, R., & Somchit, M. N. (2020) · Biomolecules · doi:10.3390/biom10020280 · Cited by 16
“However, being a classic non-selective nociceptive model, drugs such as muscle relaxants and adrenergic receptor agonists can also reduce abdominal constriction, which could lead to a false positive conclusion [25].”
Background
Asprosin, a novel therapeutic candidate for painful neuropathy: an experimental study in mice
Özcan, S., Keleştemur, M. M., Hekım, M. G., Bulmuş, Ö., Bulut, F., Bılgın, B., Canpolat, S., & Özcan, M. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-021-02197-w · Cited by 16
The galactosylation of Nω-nitro-L-arginine enhances its anti-nocifensive or anti-allodynic effects by targeting glia in healthy and neuropathic mice
Giordano, C., Siniscalco, D., Melisi, D., Luongo, L., Curcio, A., Soukupovà, M., Palazzo, E., Marabese, I., Chiaro, M. D., Rimoli, M. G., et al. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.01.045 · Cited by 16
Pharmacological effects of primaquine ureas and semicarbazides on the central nervous system in mice and antimalarial activity in vitro
Kędzierska, E., Orzelska‐Górka, J., Perković, I., Knežević, D., Fidecka, S., Kaiser, M., & Zorc, B. (2015) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12161 · Cited by 16
Antinociceptive Activity of Ent‐Dihydrotucumanoic Acid Isolated from Gymnosperma glutinosum Spreng Less
Alonso‐Castro, Á. J., González‐Chávez, M. M., Zapata‐Morales, J. R., Portales, A. K. V., Sánchez‐Recillas, A., Ortíz‐Andrade, R., Isiordia‐Espinoza, M. A., Martínez‐Gutiérrez, F., Ramírez‐Morales, M. A., Domínguez, F., et al. (2017) · Drug Development Research · doi:10.1002/ddr.21397 · Cited by 16
“…compared to the positive control IND. DTA was assessed in two tests of nociception, (1) the formalin test which evaluates peripherally and centrally acting antinociceptive agents, and the acetic acid writhing test, which assesses peripherally acting antinociceptive drugs [Le Bars et al., 2001].”
Method
Evaluation of anti-nociceptive, anti-inflammatory and antipyretic potential of Mikania cordata (Burm. f.) Robinson in experimental animal model
Siddiqui, S. A., Rahman, A., Rahman, M. O., Akbar, M. A., Rouf, A. S. S., Ali, M. A., Al-Hemaid, F. M. A., & Farah, M. A. (2018) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2018.01.009 · Cited by 16
Characterisation of the in vivo interactions between detomidine and methadone in horses: Pharmacokinetic and pharmacodynamic modelling
Gozalo‐Marcilla, M., Luna, S. P. L., da Silva, R. M., Crosignani, N., Lopes, N. P., Taylor, P. M., & Pelligand, L. (2018) · Equine Veterinary Journal · doi:10.1111/evj.13031 · Cited by 16
“electrical nociceptive Aδ and C, and the Aβ not directly involved in antinociception; thermal - mainly C fibres; mechanical - both Aδ and C) [24].”
Background
Neuropathic pain models and outcome measures: a dual translational challenge
Sewell, R. D. E. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.09.58 · Cited by 16
Vernonia polysphaera Baker: Anti-inflammatory activity in vivo and inhibitory effect in LPS-stimulated RAW 264.7 cells
Oliveira, I. D. S. D. S., Colares, A. V., Cardoso, F. D. O., Moragas-Tellis, C. J., Chagas, M. D. S. D. S., Behrens, M. D., Calabrese, K. D. S., Almeida-Souza, F., & Abreu‐Silva, A. L. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225275 · Cited by 16
“The paw edema was determined by the modified Le Bars et al (2001) method)[16].”
Method
Pharmacological Evaluation of Artemisia cina Crude CO2 Subcritical Extract after the Removal of Santonin by Means of High Speed Countercurrent Chromatography
Sakipova, Z., Giorno, T. B. S., Bekezhanova, T. S., Wong, N. S. H., Shukirbekova, A., Fernandes, P. D., & Boylan, F. (2020) · Molecules · doi:10.3390/molecules25122728 · Cited by 16
“The second phase, on the other hand, is the period of sensitization [36] where the peripheral nerve fibers are stimulated to induce pain [37].”
Background
Transcranial Direct Current Stimulation (tDCS) Induces Analgesia in Rats with Neuropathic Pain and Alcohol Abstinence
Santos, D. S., Lopes, B. C., Medeiros, L. F., Assumpção, J. A. F., de Souza, A., Salvi, A. A., da Silva, L. S., Fregni, F., Caumo, W., & Torres, I. L. D. S. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03116-w · Cited by 16
“While the nociceptive threshold is the latency of response to the nociception stimulus, hyperalgesia is an abnormal increase in the sensitivity to nociceptive stimuli, including different activation of fibers and supraspinal responses triggered by each test [65].”
Background
Shortened derivatives from native antimicrobial peptide LyeTx I: In vitro and in vivo biological activity assessment
Fuscaldi, L. L., Júnior, J. T. D. A., dos Santos, D. M., Boff, D., de Oliveira, V. L. S., Gomes, K. A. G. G., Cruz, R. D. C., de Oliveira, P. L., Magalhães, P. P., Cisalpino, P. S., et al. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220966963 · Cited by 16
“Thus, for animals, the most suitable term is nociception or hypernociception.(31) In this sense, we measured the removal threshold hypernociception, which is the maximum pressure in the infected paw tolerated by mice after which animals remove it.”
Background
Evaluation of Analgesic and Anti-inflammatory Potential of 80% Methanol Leaf Extract of Otostegia integrifolia Benth (Lamiaceae)
Tesfaye, R., Degu, A., Abebe, B., & Ayalew, H. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s285932 · Cited by 16
“These peptides such as met-enkephalin and leu-enkephalin, and βendorphin along with their cognate receptors are integral parts of the pain modulatory circuit expressed in the brain and across the pain pathways.(39) One of the classic tools for the assessment of peripheral analgesia is acetic acid induced writhing meth…”
Background
Lamiaceae in Mexican Species, a Great but Scarcely Explored Source of Secondary Metabolites with Potential Pharmacological Effects in Pain Relief
Hernández-León, A., Moreno-Pérez, G. F., Martínez-Gordillo, M. J., Aguirre-Hernández, E., Valle-Dorado, M. G., Díaz‐Reval, I., González-Trujano, M. E., & Pellicer, F. (2021) · Molecules · doi:10.3390/molecules26247632 · Cited by 18
Antinociceptive and antiulcer activities of Pycnanthus angolensis
Sofidiya, M. O., & Awolesi, A. O. (2015) · Revista Brasileira de Farmacognosia · doi:10.1016/j.bjp.2015.05.004 · Cited by 16
Corticosterone does not change open elevated plus maze-induced antinociception in mice
Mendes-Gomes, J., Miguel, T. T., Amaral, V. C. S., & Nunes‐de‐Souza, R. L. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.07.004 · Cited by 16
“This phase is caused by C-fiber activation (McCall et al., 1996; Tjolsen et al., 1992) and also involves a period of sensitization during which inflammatory phenomena occur (Le Bars et al., 2001; Tjolsen et al., 1992).”
Metabotropic glutamate antagonists alone and in combination with morphine
Picker, M. J., Daugherty, D., Henry, F. E., Miller, L. L., & Dykstra, L. (2011) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32834d13a2 · Cited by 16
“Moreover, the nociceptive response observed in acute and chronic pain models is mediated by distinct pain fibers and subserved by distinct excitatory amino acids and neurotransmitter systems (Le Bars et al., 2001; Kayser et al., 2007).”
Background
Antinociceptive activity of 3-O-β-d-glucopyranosyl-23,24-dihydrocucurbitacin F from Hintonia standleyana (Rubiaceae)
Déciga‐Campos, M., Guerrero‐Analco, J. A., Quijano, L., & Mata, R. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.02.020 · Cited by 16
“Two well known animal models were used in this study to accomplish such endeavor, the writhing and the hot-plate tests (Woolfe and MacDonald, 1944; Eddy and Leimbach, 1953; Collier et al., 1968; Chiang and Zhuo, 1989; Le Bars et al., 2001).”
The glycine site-specific NMDA antagonist (+)-HA966 enhances the effect of morphine and reverses morphine tolerance via a spinal mechanism
Adam, F., Dufour, E., & Bars, D. L. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.11.013 · Cited by 16
Intrathecal injection of lentivirus‐mediated glial cell line‐derived neurotrophic factor RNA interference relieves bone cancer‐induced pain in rats
Meng, F., Xu, Y. X. Z., Dan, Q., Wei, L., Deng, Y., Liu, J., He, M., Liu, W., Xia, Q., Zhou, F. H., et al. (2015) · Cancer Science · doi:10.1111/cas.12609 · Cited by 17
Growing Pains: Development of the Larval Nocifensive Response in Drosophila
Sulkowski, M. J., Kurosawa, M. S., & Cox, D. N. (2011) · Biological Bulletin · doi:10.1086/bblv221n3p300 · Cited by 16
“Drosophila has emerged as an exceptionally powerful genetic and behavioral model system in which to investigate the molecular underpinnings of nociception and nociceptive sensitization (Tracey et al., 2003; Maney and Dimitrijevic, 2004; Babcock et al., 2009).”
Background
An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac
Woode, E., Ameyaw, E. O., Abotsi, W. K. M., & Boakye‐Gyasi, E. (2015) · Journal of Basic and Clinical Pharmacy · doi:10.4103/0976-0105.168055 · Cited by 16
Antitussive, expectorant and analgesic effects of the ethanol seed extract of Picralima nitida (Stapf) Th. & H. Durand.
Dapaah, G., Koffuor, G. A., Mante, P. K., & Ben, I. O. (2016) · PubMed Central · Cited by 16
Design, synthesis and pharmacological evaluation of new anti-inflammatory compounds
Cidade, A. F., Vasconcelos, P. A., da Silva, D. P. B., Florentino, I. F., Vasconcelos, G. A., Vaz, B. G., Costa, É. A., Lião, L. M., & Menegatti, R. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.08.033 · Cited by 16
“The acetic acid induced writhing test has a good sensitivity to evaluate agents with anti-nociceptive activity and also agents with others pharmacological proprieties and, therefore it isn’t a test with good specificity (Le Bars et al., 2001).”
Background
In vivo analgesic, anti-inflammatory and antioxidant potentials of Achillea odorata from north Algeria
Boutennoun, H., Boussouf, L., Kebieche, M., Al-Qaoud, K. M., & Madani, K. (2017) · South African Journal of Botany · doi:10.1016/j.sajb.2017.06.004 · Cited by 17
Evidence for the involvement of TNF-α, IL-1β and IL-10 in the antinociceptive and anti-inflammatory effects of indole-3-guanylhydrazone hydrochloride, an aromatic aminoguanidine, in rodents
Sandes, S. M. S., Heimfarth, L., de Brito, R. G., Santos, P. L., Gouveia, D. N., Carvalho, A. M. D. S., Quintans, J. D. S. S., da Silva‐Júnior, E. F., de Aquino, T. M., França, P. H. B., et al. (2018) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2018.02.026 · Cited by 16
Analgesic Efficacy and Safety of Buprenorphine in Chinchillas (Chinchilla lanigera)
Fox, L., & Mans, C. (2018) · Journal of the American Association for Laboratory Animal Science · doi:10.30802/aalas-jaalas-17-000108 · Cited by 16
Oral administration of essential oil from Psidium glaziovianum Kiaersk leaves alleviates pain and inflammation in mice
Costa, W. K., do Nascimento, M. F., dos Santos, C. R. B., de Aguiar, J. C. R. D. O. F., Navarro, D. M. D. A. F., Napoleão, T. H., Correia, M. T. D. S., Brayner, F. A., de Oliveira, A. M., & da Silva, M. V. (2022) · Inflammopharmacology · doi:10.1007/s10787-022-00940-0 · Cited by 16
Involvement of Y5 receptors in neuropeptide Y agonist-induced analgesic-like effect in the rat hot plate test
Thomsen, M., Wörtwein, G., Olesen, M. V., Begtrup, M., Havez, S., Bolwig, T. G., & Woldbye, D. P. D. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.021 · Cited by 16
Interaction of memantine and ketamine in morphine- and pentazocine-induced antinociception in mice.
Malec, D., Mandryk, M., & Fidecka, S. (2008) · PubMed · Cited by 16
The Ameliorative Effect of Thymoquinone on Vincristine-Induced Peripheral Neuropathy in Mice by Modulating Cellular Oxidative Stress and Cytokine
Alenezi, S. K. (2022) · Life · doi:10.3390/life13010101 · Cited by 15
“Centrally acting analgesics reduce both the acute and delayed phases of pain response, whereas peripherally acting drugs inhibit only the delayed phase [48].”
A Non-invasive Model for Measuring Nociception after Tooth Pulp Exposure
Kramer, P. R., He, J., Puri, J., & Bellinger, L. L. (2012) · Journal of Dental Research · doi:10.1177/0022034512454297 · Cited by 15
“…(Chattipakorn et al., 2002); behavioral changes in abnormal head movement, shaking of lower jaw, and rubbing of the mouth (Chidiac et al., 2002); exploring, freezing, and yawning (Chudler and Byers, 2005); and indirect measures of nociception with Von Frey filaments or heat (Le Bars et al., 2001).”
Background
Chemical restraint and anaesthetic effects of a tiletamine–zolazepam/ketamine/detomidine combination in cattle
Re, M. T., Blanco-Murcia, J., & de Segura, I. Á. G. (2010) · The Veterinary Journal · doi:10.1016/j.tvjl.2010.09.023 · Cited by 15
Evaluation of antinociceptive effect of methanolic leaf and root extracts of Clitoria ternatea Linn. in rats
Kamilla, L., Ramanathan, S., Sasidharan, S., & Mansor, S. (2014) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.140583 · Cited by 15
“The hot plate responses (paw-licking) is considered to be mediated by complex supraspinally organized behavior.[9,15] Seeing that both the C.”
Antinociceptive effect of semi-purified petroleum ether partition of Muntingia calabura leaves
Zakaria, Z. A., Sani, M. H. M., Kadir, A. A., Teh, L. K., & Salleh, M. Z. (2016) · Revista Brasileira de Farmacognosia · doi:10.1016/j.bjp.2015.12.007 · Cited by 15
Nimodipine is more effective than nifedipine in attenuating morphine tolerance on chronic co-administration in the rat tail-flick test.
Ray, S. B., Mishra, P., Verma, D., Gupta, A., & Wadhwa, S. (2008) · PubMed · Cited by 15
The Contribution of NMDA Receptors in Antinociceptive Effect of Pregabalin: Comparison of Two Models of Pain Assessment
Meymandi, M. S., Keyhanfar, F., Sepehri, G., Heravi, G., & Yazdanpanah, O. (2017) · Anesthesiology and Pain Medicine · doi:10.5812/aapm.14602 · Cited by 15
“The hot plate test assesses acute pain by spinal and supra spinal mechanism and acetic acid induced visceral pain screens both the peripheral and central mechanisms (25).”
Background
Maternal deprivation alters nociceptive response in a gender‐dependent manner in rats
Ströher, R., de Oliveira, C., Lopes, B. C., da Silva, L. S., Regner, G. G., Medeiros, H. R., de Macedo, I. C., Caumo, W., & Torres, I. L. D. S. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.05.001 · Cited by 15
Modulation of Pain Sensitivity by Chronic Consumption of Highly Palatable Food Followed by Abstinence: Emerging Role of Fatty Acid Amide Hydrolase
Cifani, C., Avagliano, C., Bonaventura, E. M. D., Giusepponi, M. E., Caro, C. D., Cristiano, C., Rana, G. L., Botticelli, L., Romano, A., Calignano, A., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00266 · Cited by 15
Satellite Glial Cells of the Dorsal Root Ganglion: A New “Guest/Physiopathological Target” in ALS
Ruiz‐Soto, M., Riancho, J., Tapia, O., Lafarga, M., & Berciano, M. T. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.595751 · Cited by 15
Identification of a Potent and Selective 5-HT1A Receptor Agonist with In Vitro and In Vivo Antinociceptive Activity
Linciano, P., Sorbi, C., Comitato, A., Leśniak, A., Bujalska‐Zadrożny, M., Pawłowska, A., Bielenica, A., Orzelska‐Górka, J., Kędzierska, E., Biała, G., et al. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00289 · Cited by 15
Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity
Szandruk-Bender, M., Wiatrak, B., Szczukowski, Ł., Świątek, P., Rutkowska, M., Dzimira, S., Merwid‐Ląd, A., Danielewski, M., & Szeląg, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249685 · Cited by 15
“It is noteworthy that compared to other models of thermal stimulation, the tail-flick test does not elicit tactile stimulus because beaming heat constitutes a relatively selective stimulus for nociceptors [12].”
BackgroundMethodResultInfluential
Antioxidant, Anti-inflammatory, and Analgesic Activities of Alcoholic Extracts of Ephedra nebrodensis From Eastern Algeria
Hamoudi, M., Amroun, D., Baghiani, A., Khennouf, S., & Dahamna, S. (2021) · Turkish Journal of Pharmaceutical Sciences · doi:10.4274/tjps.galenos.2021.24571 · Cited by 16
“Activation of prostaglandins, histamines, serotonin, lipooxygenases, cyclooxygenases and endogenous cytokines (IL-8 and IL-1β), in peripheral tissue was activated by acetic acid injection into abdominal cavity of mice [44], which often penetrates the dorsal horn of the CNS (central nervous system) and stimulates prima…”
Background
Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors
Tewari, D., Gupta, P. K., Bawari, S., Sah, A. N., Barreca, D., Khayatkashani, M., & Kashani, H. R. K. (2021) · Plants · doi:10.3390/plants10081685 · Cited by 15
“The hot plate model is believed to be more complex than the tail-flick model, due to paw licking and jumping responses, which are the two important behavioral components and are considered to be supraspinally integrated [28,29].”
Background
Pain Testing in the Laboratory Mouse
Langford, D. J., & Mogil, J. S. (2008) · Elsevier eBooks · doi:10.1016/b978-012373898-1.50027-9 · Cited by 15
Effects of aloperine on acute and inflammatory pain models in mice
Yang, Y., Jin, S., Wang, H., Li, Y., Du, J., Zhou, R., Zheng, J., Ma, L., Zhao, C., Niu, Y., et al. (2015) · Scandinavian Journal of Pain · doi:10.1016/j.sjpain.2015.04.001 · Cited by 15

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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