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Antinociceptive and neurochemical effects of a single dose of IB-MECA in chronic pain rat models

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Abstract

This study aimed to evaluate the effect of a single administration of IB-MECA, an A3 adenosine receptor agonist, upon the nociceptive response and central biomarkers of rats submitted to chronic pain models. A total of 136 adult male Wistar rats were divided into two protocols: (1) chronic inflammatory pain (CIP) using complete Freund’s adjuvant and (2) neuropathic pain (NP) by chronic constriction injury of the sciatic nerve. Thermal and mechanical hyperalgesia was measured using von Frey (VF), Randal-Selitto (RS), and hot plate (HP) tests. Rats were treated with a single dose of IB-MECA (0.5 μmol/kg i.p.), a vehicle (dimethyl sulfoxide—DMSO), or positive control (morphine, 5 mg/kg i.p.). Interleukin 1β (IL-1β), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels were measured in the brainstem and spinal cord using enzyme-linked immunosorbent assay (ELISA). The establishment of the chronic pain (CIP or NP) model was observed 14 days after induction by a decreased nociceptive threshold in all three tests (GEE, P < 0.05). The antinociceptive effect of a single dose of IB-MECA was observed in both chronic pain models, but this was more effective in NP model. There was an increase in IL-1β levels promoted by CIP. NP model promoted increase in the brainstem BDNF levels, which was reversed by IB-MECA

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Authors and Affiliations

  1. Laboratório de Farmacologia da Dor e Neuromodulação, Investigações Pré-clínicas, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil

    Stefania Giotti Cioato, Liciane Fernandes Medeiros, Bettega Costa Lopes, Andressa de Souza, Helouise Richardt Medeiros, José Antônio Fagundes Assumpção & Iraci L. S. Torres

  2. Unidade de Experimentação Animal, Grupo de Pesquisa e Pós-Graduação, HCPA, Porto Alegre, RS, Brazil

    Stefania Giotti Cioato, Liciane Fernandes Medeiros, Bettega Costa Lopes, Helouise Richardt Medeiros, José Antônio Fagundes Assumpção & Iraci L. S. Torres

  3. Programa de Pós-Graduação em Ciências Biológicas, Farmacologia e Terapêutica, Instituto de Ciências Básicas da Saúde (ICBS), UFRGS, Porto Alegre, RS, Brazil

    Stefania Giotti Cioato, Liciane Fernandes Medeiros, José Antônio Fagundes Assumpção, Rafael Roesler & Iraci L. S. Torres

  4. Programa de Pós-Graduação em Saúde e Desenvolvimento Humano, Universidade La Salle, Canoas, RS, Brazil

    Liciane Fernandes Medeiros & Andressa de Souza

  5. Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, ICBS, UFRGS, Porto Alegre, RS, Brazil

    Bettega Costa Lopes

  6. Programa de Pós-Graduação em Medicina, Ciências Médicas, UFRGS, Porto Alegre, RS, Brazil

    Helouise Richardt Medeiros, Wolnei Caumo, Rafael Roesler & Iraci L. S. Torres

  7. Cancer and Neurobiology Laboratory, Experimental Research Center, HCPA, Porto Alegre, RS, Brazil

    Rafael Roesler

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  1. Stefania Giotti Cioato
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  2. Liciane Fernandes Medeiros
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  9. Iraci L. S. Torres
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Correspondence to Iraci L. S. Torres.

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Conflicts of interest

Stefania Giotti Cioato declares that she has no conflict of interest. Liciane Fernandes Medeiros declares that she has no conflict of interest. Bettega Costa Lopes declares that he has no conflict of interest. Andressa de Souza declares that she has no conflict of interest. Helouise Richardt Medeiros declares that she has no conflict of interest. José Antônio Fagundes Assumpção declares that he has no conflict of interest. Wolnei Caumo declares that he has no conflict of interest. Rafael Roesler declares that he has no conflict of interest. Iraci L. S. Torres declares that she has no conflict of interest.

Ethical approval

This study was approved by the Institutional Animal Care and Use Committee (GPPG-HCPA protocol no. 150530 and no.2018-0377).

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Cioato, S.G., Medeiros, L.F., Lopes, B.C. et al. Antinociceptive and neurochemical effects of a single dose of IB-MECA in chronic pain rat models. Purinergic Signalling 16, 573–584 (2020). https://doi.org/10.1007/s11302-020-09751-w

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