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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Method
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Background
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Tomic´, M. A., Vučković, S., Stepanović-Petrović, R. M., Ugrešić, N. D., Prostran, M. S., & Bošković, B. (2010) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181cbd8da · Cited by 21
Effects of ketamine on acute somatic nociception in wild-type and N-methyl-d-aspartate (NMDA) receptor ɛ1 subunit knockout mice
Petrenko, A. B., Yamakura, T., Askalany, A. R., Kohno, T., Sakimura, K., & Baba, H. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.019 · Cited by 21
Psychophysics of a Nociceptive Test in the Mouse: Ambient Temperature as a Key Factor for Variation
Pincedé, I., Pollin, B., Meert, T. F., Plaghki, L., & Bars, D. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036699 · Cited by 21
“We believe that such an approach satisfies the repeated requests for improving nociceptive tests [2,47,49,51,57] and offers potentially heuristic progress for studying nociception on firmer physiological, behavioral and psychophysical grounds with the same approach in man and animals, this latter now including species…”
Background
Voluntary Running-Wheel Activity, Arterial Blood Gases, and Thermal Antinociception in Rats after 3 Buprenorphine Formulations.
Johnson, R. A. (2016) · PubMed Central · Cited by 21
Rodent Gymnastics: Neurobehavioral Assays in Ischemic Stroke
Nampoothiri, S. S., Potluri, T., Subramanian, H., & Rajanikant, G. K. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0195-6 · Cited by 21
A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems
Pacheco, D. D. F., Freitas, A. C. N., Pimenta, A. M. C., Duarte, I. D. G., & de Lima, M. E. (2016) · The Journal of venomous animals and toxins including tropical diseases · doi:10.1186/s40409-016-0091-6 · Cited by 21
“avoid tissue damage, the cutoff time was established at 9 s [19].”
Background
Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice
Moreira, C. D. L. F. A., Pinheiro, J. G. D. O., Júnior, W. F. D. S., Barbosa, E. G., Lavra, Z. M. M., Pereira, E. W. M., Rezende, M. M., de Azevedo, E. P., Quintans‐Júnior, L. J., Araújo, A. A. D. S., et al. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.10.161 · Cited by 21
Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals
Jin, H. Y., Moon, S., & Calcutt, N. A. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2020.0216 · Cited by 22
“Sensory perception and pain Behavioral responses to sensory stimuli are widely used as surrogates of presumed pain perception in diabetic rodents, with all the attendant caveats that apply to use of such evoked response tests when used to define other models of neuropathic pain [123,124].”
Background
The novel analgesic, F 13640, produces intra- and postoperative analgesia in a rat model of surgical pain
Kiss, I. E., Degryse, A. A. Y., Bardin, L., de Segura, I. Á. G., & Colpaert, F. C. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.09.003 · Cited by 21
Experimental study on antinociceptive and anti-allergy effects of patchouli oil
He, J., Chen, H., Li, C., Wu, D.-W., Wu, X., Shi, S., Li, Y., Chen, J., Su, Z., & Lai, X. (2013) · Journal of Essential Oil Research · doi:10.1080/10412905.2013.809319 · Cited by 21
Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides μ1 receptor-mediated post-ictal antinociception
Felippotti, T. T., do Carmo, D. R., Paim, L. L., Stradiotto, N. R., Bicalho, U. D. O., Parada, C. A., Grillo, R., Fraceto, L. F., & Coimbra, N. C. (2011) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2011.02.005 · Cited by 21
Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain
Dürsteler, C., Miranda, H. F., Poveda, R., Mases, A., Planas, E., & Puig, M. M. (2007) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2007.00511.x · Cited by 22
The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist
Montes, G. C., Silva, B. D., Rezende, B., Sudo, R. T., Ferreira, V. F., da Silva, F. D. C., Pinto, Â. D. C., da Silva, B. V., & Zapata‐Sudo, G. (2017) · Molecules · doi:10.3390/molecules22050800 · Cited by 20
“Our results demonstrated that PILAB 8 inhibited both phases of the formalin-induced nociception test, thus a noxious thermal stimulus induced by a hot plate was used to investigate the analgesic drug action [33,41].”
Result
Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep
Marini, D., Pippia, J., Colditz, I. G., Hinch, G. N., Petherick, J. C., & Lee, C. (2015) · Australian Veterinary Journal · doi:10.1111/avj.12351 · Cited by 20
Regulation of Neuropathic Hypersensitivity by α2‐Adrenoceptors in the Pontine A 7 Cell Group
Wei, H., & Pertovaara, A. (2012) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2012.00930.x · Cited by 20
Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice
Onasanwo, S. A., Oyagbemi, A. A., & Saba, A. B. (2011) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp.2011.010 · Cited by 20
“The intraperitoneal administration of acetic acid irritates serous membranes and has been shown to provoke stereotypical behavior in mice, which is characterized by abdominal contractions, movements of the body as a whole, twisting of dorso-abdominal muscles, and a reduction in motor activity and coordination (25) .”
Background
Extracts from the leaves of Campomanesia velutina inhibits production of LPS/INF-γ induced inflammatory mediators in J774A.1 cells and exerts anti-inflammatory and antinociceptive effects in vivo
Michel, M. C. P., Grabe‐Guimarães, A., Paula, C. A., Rezende, S. A., Sobral, M., & Guimarães, D. A. S. (2013) · Revista Brasileira de Farmacognosia · doi:10.1590/s0102-695x2013000600010 · Cited by 20
“This model of nociception is a sensitive and specific test used to show the involvement of central mechanisms (Le Bars et al., 2001).”
Background
Opioid system mediated anti-nociceptive effect of agomelatine in mice
Kasap, M., & Can, Ö. D. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.08.031 · Cited by 21
Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one in Mice Models of Induced Nociception
Ismail, N., Lee, M. T., Lajis, N. H., Akhtar, M. N., Akira, A., Perimal, E. K., Israf, D. A., & Sulaiman, M. R. (2016) · Molecules · doi:10.3390/molecules21081077 · Cited by 20
“This result also substantiates the results observed in formalin- and capsaicin-induced paw-licking tests, as both studies show that there is an increased level of glutamate as well as NO due to the stimulation of afferent C-fibers following injection of formalin or capsaicin into the paw [22,30,42].”
BackgroundMethodResultInfluential
Antinociceptive effects of the 6- O -sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors
Yadlapalli, J. S. K., Ford, B. M., Ketkar, A. D., Wan, A., Penthala, N. R., Eoff, R. L., Prather, P. L., Dobretsov, M. G., & Crooks, P. A. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.09.012 · Cited by 20
“Baseline characteristics of control and STZ-treated rats—For comparison of the antinociceptive effects of M6S and morphine in vivo in normal and diabetic rats, the hot water tail-flick latency (TWL) test was selected due to its simplicity and sensitivity for evaluation of antinociception in response to thermal pain [3…”
Method
Unconventional Role of Caspase-6 in Spinal Microglia Activation and Chronic Pain
Berta, T., Lee, J. E., & Park, C. (2017) · Mediators of Inflammation · doi:10.1155/2017/9383184 · Cited by 20
Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models
Boakye‐Gyasi, E., Henneh, I. T., Abotsi, W. K. M., Ameyaw, E. O., & Woode, E. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1750-z · Cited by 20
“Though acetic acid-induced writhing test can detect both weak and strong analgesics, it equally detects some non-analgesics such as antihistamines, muscle relaxants, monoamine oxidase inhibitors among others [41, 45] and this has been an important limitation of the test.”
BackgroundInfluential
Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments
Almeida, L. E. F., Kamimura, S., Batista, C. M. D. S., Spornick, N., Nettleton, M. Y., Walek, E., Smith, M. L., Finkel, J. C., Darbari, D. S., Wakim, P., et al. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.10.011 · Cited by 20
“We examined nocifensive response to thermal (hotplate and cold plate sensitivity) and electrical stimuli (sensory fiber interrogation) [37; 38; 39; 40; 41].”
Method
Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin test
Savegnago, L., Jessé, C. R., Santos, A. R. S., da Rocha, J. B. T., & Nogueira, C. W. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.12.0015 · Cited by 20
“The formalin model was chosen for this purpose because of the specificity and sensitivity in nociception transmission that this model provides (Le Bars et al 2001).”
Method
Anti-Nociceptive Effects of an Ethanolic Extract of the Whole Plant of Synedrella nodiflora (L.) Gaertn in Mice: Involvement of Adenosinergic Mechanisms
Woode, E., Amoateng, P., Ansah, C., & Duwiejua, M. (2008) · Journal of Pharmacology and Toxicology · doi:10.3923/jpt.2009.17.29 · Cited by 20
Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation
Levionnois, O., Spadavecchia, C., Kronen, P., & Schatzmann, U. (2008) · Veterinary Anaesthesia and Analgesia · doi:10.1111/j.1467-2995.2008.00420.x · Cited by 20
Antinociceptive tolerance to NSAIDs in the rat formalin test is mediated by the opioid mechanism
Tsiklauri, N., Nozadze, I., Gurtskaia, G., & Tsagareli, M. G. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.10.004 · Cited by 20
Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test
Roca-Vinardell, A., Berrocoso, E., Llorca-Torralba, M., Garcia-Partida, J. A., Gibert‐Rahola, J., & Micó, J. A. (2018) · Neurobiology of Pain · doi:10.1016/j.ynpai.2018.01.004 · Cited by 20
“Moreover, many data indicate that locomotion may influence nociception, but the changes have not always been well elucidated (Le Bars et al., 2001).”
Background
Prenylated β-diketones, two new additions to the family of biologically active Hypericum perforatum L. (Hypericaceae) secondary metabolites
Radulović, N. S., Genčić, M. S., Stojanović, N. M., Randjelović, P. J., Baldovini, N., & Kurteva, V. B. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.05.009 · Cited by 20
Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization
Vandeputte, M. M., Bilel, S., Tirri, M., Corli, G., Bassi, M., Layle, N. K., Fantinati, A., Walther, D., Iula, D. M., Baumann, M. H., et al. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110113 · Cited by 19
The flavonol-enriched Cistus albidus chloroform extract possesses in vivo anti-inflammatory and anti-nociceptive activity
Tahiri, O., Atmani-Kilani, D., Sánchez‐Fidalgo, S., Aparicio‐Soto, M., Alarcón‐de‐la‐Lastra, C., Barrajón‐Catalán, E., Micol, V., & Atmani, D. (2017) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2017.07.012 · Cited by 19
Evaluation of the Thermal Antinociceptive Effects of a Sustained-Release Buprenorphine Formulation After Intramuscular Administration to American kestrels ( Falco sparverius )
Guzman, D. S.-M., Ceulemans, S. M., Beaufrère, H., Olsen, G. H., & Paul‐Murphy, J. (2018) · Journal of Avian Medicine and Surgery · doi:10.1647/2016-190 · Cited by 19
Anti-Inflammatory, Antipyretic, and Analgesic Properties of Potamogeton perfoliatus Extract: In Vitro and In Vivo Study
Rezq, S., Mahmoud, M. F., El-Shazly, A. M., Raey, M. A. E., & Sobeh, M. (2021) · Molecules · doi:10.3390/molecules26164826 · Cited by 19
Dimethyl Itaconate Attenuates CFA-Induced Inflammatory Pain via the NLRP3/ IL-1β Signaling Pathway
Lin, J., Ren, J., Zhu, B., Dai, Y., Gao, D. S., Xia, S., Cheng, Z., Huang, Y., & Yu, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.938979 · Cited by 19
“Macrophages produce various in ammatory mediators, such as in ammatory cytokines, growth factors, and lipids after tissue injury and infection, directly leading to primary hyperalgesia at sites of injury or in ammation [9, 10].”
Background
Thymus hirtus Willd. ssp. algeriensis Boiss. and Reut: A Comprehensive Review on Phytochemistry, Bioactivities, and Health-Enhancing Effects
Lahlou, R. A., Samba, N., Soeiro, P. F., Alves, G., Gonçalves, A. C., Silva, L. R., Silvestre, S., Rodilla, J. M., & Ismael, M. I. (2022) · Foods · doi:10.3390/foods11203195 · Cited by 22
An automated rat grimace scale for the assessment of pain
Arnold, B., Ramakrishnan, R., Wright, A., Wilson, K. A., & VandeVord, P. J. (2023) · Scientific Reports · doi:10.1038/s41598-023-46123-x · Cited by 19
Analgesic activity ofGleditsia triacanthosmethanolic fruit extract and its saponin-containing fraction
Saleh, D. O., Kassem, I. A. A., & Melek, F. R. (2015) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1064450 · Cited by 19
“…shortcoming of the writhing test is that it lacks specificity as it works for other substances and classes of drugs including some that have no analgesic action, e.g., adrenergic blockers, antihistamines, muscle relaxants, monoamine oxidase inhibitors, and neuroleptics (Le Bars et al., 2001).”
Background
Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome
Muncey, A. R., Saulles, A., Koch, L. G., Britton, S. L., Baghdoyan, H. A., & Lydic, R. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181f56248 · Cited by 21
Potential mechanisms for hypoalgesia induced by anti-nerve growth factor immunoglobulin are identified using autoimmune nerve growth factor deprivation
Hoffman, E. M., Zhang, Z., Anderson, M. C., Schechter, R., & Miller, K. E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.069 · Cited by 19
“While slow heating with the thermal latency test can detect hypoalgesia (Lu et al., 1997), the test was designed and is most suitable for measuring hyperalgesic phenomena (Hargreaves et al., 1988, Le Bars et al., 2001) and may be why it did not detect hypoalgesia in the current study.”
Method
Medullary monoamines and NMDA-receptor regulation of cardiovascular responses during peripheral nociceptive stimuli
Karlsson, G. A., Preuss, C. V., Chaitoff, K. A., Maher, T. J., & Ally, A. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.04.002 · Cited by 19
Effects of tapentadol on mechanical hypersensitivity in rats with ligatures of the infraorbital nerve versus the sciatic nerve
Michot, B., Bourgoin, S., Kayser, V., & Hamon, M. (2012) · European Journal of Pain · doi:10.1002/j.1532-2149.2012.00259.x · Cited by 21
“As PW is a spinally coordinated reflex whereas vocalization is a supra-spinal integrated response (Le Bars et al., 2001), this test can provide some indirect indications on the respective contributions of spinal versus supra-spinal mechanisms in the modulatory effects of drugs on nociceptive…”
Background
Evaluation of the analgesic and anti-inflammatory activity of Moringa concanensis tender fruits
Rao, V., Hussain, T., Verma, A. R., Kumar, N. S., Vijayakumar, M., & Marg, R. P. (2008) · 亚洲传统医药 · Cited by 19
Locomotor Activity in a Novel Environment as a Test of Inflammatory Pain in Rats
Matson, D. J., Broom, D. C., & Cortright, D. N. (2010) · Methods in molecular biology · doi:10.1007/978-1-60327-323-7_6 · Cited by 19
Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids
Kuramoto, K., Wang, N., Fan, Y., Zhang, W., Schoenen, F. J., Frankowski, K. J., Marugán, J., Zhou, Y., Huang, S., & He, C. (2016) · Autophagy · doi:10.1080/15548627.2016.1187367 · Cited by 19
New Horizons in Pharmacologic Treatment for Rheumatic Disease Pain
Dray, A. (2008) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2008.04.005 · Cited by 19
“In a similar vein, models of neuropathic pain have involved peripheral nerve lesions [25,26].”
Nocifensive behaviors components evoked by brief laser pulses are mediated by C fibers
Fan, R., Kung, J.-C., Olausson, B., & Shyu, B. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.04.022 · Cited by 19
“[9] proposed that stimulus intensity can determine which type of nerve fiber initiates the reaction [9].”
Background
Acute toxicity, antinociceptive activity and indole alkaloids of aqueous extract from bark of Aspidosperma cuspa (Kunth) Blake
Pérez, N. M., Torrico, F., & Morales, A. (2012) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2012.07.021 · Cited by 19
Interaction between Analgesic Effect of Nano and Conventional size of Zinc Oxide and Opioidergic System Activity in Animal Model of Acute Pain.
Kesmati, M., & Torabi, M. (2014) · PubMed Central · Cited by 19
Evaluation of antinociceptive and antidiarrhoeal properties ofManilkara zapotaleaves in Swiss albino mice
Ganguly, A., Mahmud, Z. A., Saha, S. K., & Rahman, S. M. A. (2016) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1103757 · Cited by 19
“However, true antinociceptive activity can only be ensured by the combination of at least two methods as the acetic acid-induced abdominal constriction test can provide false positive results (Le Bars et al. 2001; Mohanta et al. 2013).”
Background
Cholinergic activation affects the acute and chronic antinociceptive effects of morphine
Gaweł, K., Gibuła‐Tarłowska, E., Dziedzic, M., Jenda, M., Marszałek‐Grabska, M., Silberring, J., & Kotlinska, J. H. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.11.011 · Cited by 19
Hybrid gels by conjugation of hyaluronic acid with poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)undecane) copolymers
Chiriac, A. P., Nita, L. E., Ghilan, A., Bercea, M., Tudorachi, N., Pamfil, D., & Mititelu-Tarțău, L. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.01.116 · Cited by 19
Reduced pain sensitivity in mice lacking latexin, an inhibitor of metallocarboxypeptidases
Jin, M., Ishida, M., Fukui, Y., Tsuchiya, R., Higashinakagawa, T., Ikegami, S., & Arimatsu, Y. (2006) · Brain Research · doi:10.1016/j.brainres.2005.12.099 · Cited by 19
Antioxidant, analgesic and anti-inflammatory properties of new ninhydrin adduct of embelin
Sekar, M., Badami, S., Ravi, S., Thippeswamy, B. S., & Veerapur, V. P. (2011) · Pharmaceutical Chemistry Journal · doi:10.1007/s11094-011-0676-x · Cited by 19
Tolerance to morphine analgesia: Evidence for stimulus intensity as a key factor and complete reversal by a glycine site-specific NMDA antagonist
Adam, F., Bonnet, F. J., & Bars, D. L. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.03.018 · Cited by 19
Neuropharmacological study of Argemone mexicana Linn.
Chaudhari, S., Sneha, J. A., & Anarthe, S. (2011) · Cited by 19

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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