Brazilian Journal of Pain
Brazilian Journal of Pain
Review Article

In vivo methods for the evaluation of anti-inflammatory and antinoceptive potential

Métodos in vivo para avaliação do potencial anti-inflamatório e antinociceptivo

Silvio de Almeida Junior

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BACKGROUND AND OBJECTIVES: The constant search for bioactive compounds with anti-inflammatory and antinociceptive activities are of interest to research centers. For the characterization of these activities, trials on guinea pigs are necessary. Therefore, the purpose of this study was to demonstrate some methods to evaluate the anti-inflammatory and antinociceptive potential of natural products.

CONTENTS: A stimulus is required to evaluate these activities, and the induction of inflammatory or nociceptive process can be by chemical inducers like formaldehyde, carrageenan, among others, or electronic equipment such as the hot plate. For all assays, the baseline and post-dose measurement of the studied compound is always compared with a control group. The planning of the experiment, as well as its conduct in accordance with well-established protocols, are important tools in the success of the work. The tests presented evaluated the antinociceptive and anti-inflammatory activity as well as the mechanisms involved.

CONCLUSION: It was possible to evaluate that the tests present in the literature today meet the researcher’s need for the elucidation of the anti-inflammatory and antinociceptive activity of new compounds.


Abdominal contortion, Formalin, Hot plate, Paw edema


JUSTIFICATIVA E OBJETIVOS: A busca constante por compostos bioativos com atividade anti-inflamatória e antinociceptiva são de interesse dos centros de pesquisas. Para a caracterização dessas atividades são necessários ensaios em cobaias. Frente a isso, o objetivo deste estudo foi demonstrar alguns métodos para a avaliação do potencial anti-inflamatório e antinociceptivo de produtos naturais.

CONTEÚDO: Para a avaliação dessas atividades é necessário um estímulo, sendo que a indução de processo inflamatório ou nociceptivo pode ser por indutores químicos como formol, carragenina, entre outros, ou ainda, equipamentos eletrônicos como placa quente. Para todos os ensaios, sempre é realizada a mensuração basal e posterior à administração do composto que está sendo estudado em comparação com um grupo controle. O planejamento do experimento, assim como toda a condução conforme protocolos já bem ilustrados, são ferramentas importantes no êxito do trabalho. Os testes apresentados avaliaram atividade antinociceptiva e anti-inflamatória assim como mecanismos envolvidos.

CONCLUSÃO: Foi possível avaliar que os testes presentes na literatura hoje, atendem a necessidade do pesquisador na elucidação da atividade anti-inflamatória e atividade antinociceptiva de novos compostos.


Contorção abdominal, Edema de pata, Formalina, Placa quente


Karasawa MMG, Mohan C. Fruits as prospective reserves of bioactive compounds: a review. Nat Prod Bioprospect. 2018;8(5):335-46.

Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015;33(8):1582-614.

Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005;78(5):431-41.

Eliaser EM, Ho JH, Hashim NM, Rukayadi Y, Ee GCL, Razis AFA. Phytochemical constituents and biological activities of melicope lunu-ankenda. Molecules. 2018;23(10).

Ibrahim N, Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S. Wound healing properties of selected natural products. Int J Environ Res Public Health. 2018;15(11).

Yuan H, Ma Q, Ye L, Piao G. The Traditional Medicine and Modern Medicine from natural products. Molecules. 2016;21(5).

Marques RG, de Miranda ML, Caetano CE, Biondo-Simões Mde L. Towards a Brazilian regimentation for use of animals in teaching and in scientific research. Acta Cir Bras. 2005;20(3):262-7.

Zuanon AC, Benjamin LA, Fonseca CC. Contribuições para a adoção de uma cultura de divulgação, valorização e de respeito aos comitês e, ou, comissões de ética no uso de animais. Rev Ceres, Viçosa. 2014;61(^sSuppl):757-63.

Batista EK, Trindade HI, Lira SR, Muller JB, Silva LL, Batista MC. Atividades antinociceptiva e anti-inflamatória do extrato etanólico de Luehea divaricata. Rev Bras Pl Med Campinas,. 2016;18(2):433-41.

Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Federation Proceedings. 1959;18:412-6.

Moreno-Quirós CV, Sánchez-Medina A, Vázquez-Hernández M, Hernández Reyes AG, García-Rodríguez RV. Antioxidant, anti-inflammatory and antinociceptive potential of Ternstroemia sylvatica Schltdl. & Cham. Asian Pac J Trop Med. 2017;10(11):1047-53.

Hunskaar S, Berge OG, Hole K. Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test. Pain. 1986;25(1):125-32.

Callegari DC, Correa JA, Pires OC, Braga RB, Gimbo AF, de Souza AA. Hyperalgesic effect of subarachnoid administration of phentolamine in mice. Rev Bras Anestesiol. 2015;65(2):111-6.

Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977;4(2):161-74.

Cazanga V, Hernandez A, Morales B, Pelissier T, Constandil L. Antinociception induced by copper salt revisited: interaction with ketamine in formalin-induced intraplantar and orofacial pain in mice. J Oral Facial Pain Headache. 2018;32(3):247-57.

Magalhães FE, Batista FL, Serpa OF, Moura LF, Lima MD, da Silva AR. Orofacial antinociceptive effect of Mimosa tenuiflora (Willd.) Poiret. Biomed Pharmacother. 2018;97:1575-85.

D'amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72(1):74-9.

Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol. 2001;76(1):45-8.

Singh P, Kongara K, Harding D, Ward N, Dukkipati VS, Johnson C. Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin. BMC Neurol. 2018;18(1):43.

Randall LO, Selitto JJ. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther. 1957;111(4):409-19.

Kiso T, Moriyama A, Furutani M, Matsuda R, Funatsu Y. Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia. Eur J Pharmacol. 2018;827:117-24.

Valdes C, Bustos G, Martinez JL, Laurido C. Antinociceptive antibiotics-loaded into solid lipid nanoparticles of prolonged release: measuring pharmacological efficiency and time span on chronic monoarthritis rats. PLoS One. 2018;13(4).

Jensen K, Andersen HO, Olesen J, Lindblom U. Pressure-pain threshold in human temporal region: Evaluation of a new pressure algometer. Pain. 1986;25(3):313-23.

Dutta R, Lunzer MM, Auger JL, Akgün E, Portoghese PS, Binstadt BA. A bivalent compound targeting CCR5 and the mu opioid receptor treats inflammatory arthritis pain in mice without inducing pharmacologic tolerance. Arthritis Res Ther. 2018;20(1):154.

Fatemi I, Amirteimoury M, Shamsizadeh A, Kaeidi A. The effect of metformin on morphine analgesic tolerance and dependence in rats. Res Pharm Sci. 2018;13(4):316-23.

Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544-7.

Beirith A, Santos AR, Calixto JB. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res. 2002;924(2):219-28.

Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol. 1996;118(4):829-38.

Zitterl-Eglseer K, Sosa S, Jurenitsch J, Schubert-Zsilavecz M, Della Loggia R, Tubaro A. Anti-oedematous activities of the main triterpendiol esters of marigold (Calendula officinalis L.). J Ethnopharmacol. 1997;57(2):139-44.

Sdayria J, Rjeibi I, Feriani A, Ncib S, Bouguerra W, Hfaiedh N. Chemical composition and antioxidant, analgesic, and anti-inflammatory effects of methanolic extract of Euphorbia retusa in mice. Pain Res Manag. 2018;2018.

Moraes ADTO, Miranda MDS, Jacob ÍTT, Amorim CADC, Moura RO, Silva SÂSD. Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives. Bioorg Med Chem. 2018;26(20):5388-96.

Khlebnicova TS, Piven YA, Baranovsky AV, Lakhvich FA, Sorokina IV, Tolstikova TG. Fluorine-containing lupane triterpenoid acid derivatives: design, synthesis and biological evaluation as potential anti-inflammatory agents. Steroids. 2019;147:62-9.

Vysakh A, Jayesh K, Helen LR, Jyothis M, Latha MS. Acute oral toxicity and anti-inflammatory evaluation of methanolic extract of Rotula aquatica roots in Wistar rats. J Ayurveda Integr Med. 2018;16.

Shabbir A, Batool SA, Basheer MI, Shahzad M, Sultana K, Tareen RB. Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. Biomed Pharmacother. 2018;97:1710-21.

Osafo N, Obiri DD, Antwi AO, Yeboah OK. The acute anti-inflammatory action of xylopic acid isolated from Xylopia aethiopica. J Basic Clin Physiol Pharmacol. 2018;29(6):659-69.

Tubaro A, Dri P, Melato M, Mulas G, Bianchi P, Del Negro P. In the croton oil ear test the effects of non steroidal antiinflammatory drugs (NSAIDs) are dependent on the dose of the irritant. Agents Actions. 1986;19(5-6):371-3.

Januario JP, de Souza TB, Lavorato SN, Maiolini TCS, Domingos OS, Baldim JL. Design and synthesis of new benzophenone derivatives with in vivo anti-inflammatory activity through dual inhibition of edema and neutrophil recruitment. Molecules. 2018;23(8).

Ferrándiz ML, Alcaraz MJ. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions. 1991;32(3-4):283-8.

Sreeja PS, Arunachalam K, Martins DTO, Lima JCDS, Balogun SO, Pavan E. Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir.: chemical characterization, anti-nociceptive and anti-inflammatory activities of methanol extract of leaves. J Ethnopharmacol. 2018;225:71-80.

Ammendola G, Di Rosa M, Sorrentino L. Leucocyte migration and lysosomal enzymes release in rat carrageenin pleurisy. Agents Actions. 1975;5(3):250-5.

Zanusso-Junior G, Melo JO, Lopes Romero AL, Dantas JA, Caparroz-Assef SM, Bersani-Amado CA. Evaluation of the anti-inflammatory activity of coriander (Coriandrum sativum L.) in rodents. Rev Bras Plantas Med. 2010;13(1):17-23.

da Silva Balin P, Zanatta FC, Jorge BC, Leitão M, Kassuya RM, Cardoso CAL. Toxicological evaluation and anti-inflammatory potential of an ethanolic extract from Bromelia balansae (Bromeliaceae) fruit. J Ethnopharmacol. 2018;222:79-86.

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