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Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+ channels

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Abstract

Objective and design

To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats.

Materials and Methods

Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg−1), DMDC (0.025, 0.25, or 2.5 µmol kg−1), biliverdin (1, 3, or 10 mg kg−1), or ZnPP-IX (1, 3 or 9 mg kg−1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg−1; s.c.) or glibenclamide (10 mg kg−1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg−1; s.c), respectively.

Results

Hemin (1 mg kg−1), DMDC (2.5 µmol kg−1), and BVD (10 mg kg−1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg−1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1β mRNA expression and immunolabelling increased.

Conclusions

HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

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Abbreviations

DMDC:

Dimethyl dicarbonate

ZnPP-IX:

Zinc protoporphyrin IX

ODQ:

1H- [1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one

TNF-α:

Tumor necrosis factor-alpha

IL-1β:

Interleukin-1beta

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Acknowledgements

This work was supported by Brazilian grants from Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Instituto de Biomedicina do Semi-Árido Brasileiro (INCT-IBISAB).

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Authors and Affiliations

  1. Faculty of Dentistry of Sobral, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100, Derby, Sobral, CEP: 62.042-280, Brazil

    Hellíada Vasconcelos Chaves & Francisco Isaac Fernandes Gomes

  2. Federal University of Pernambuco, North Eastern Biotechnology Network, Recife, Brazil

    Danielle Rocha do Val

  3. Master of Biotechnology Degree Programme, Federal University of Ceará, Sobral, Brazil

    Kátia Alves Ribeiro & Ricardo Basto Souza

  4. Faculty of Medicine, Federal University of Ceará, Sobral, Brazil

    Jonas Cavalcante Lemos, Vicente de Paulo Teixeira Pinto, Gerardo Cristino Filho & Mirna Marques Bezerra

  5. Biotechnology Research Group, State University of Acaraú Valley, Sobral, Ceará, Brazil

    Rodrigo Maranguape Silva da Cunha

  6. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil

    Marcellus Henrique Loiola Ponte de Souza & Gerly Anne de Castro Brito

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  1. Hellíada Vasconcelos Chaves
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Correspondence to Hellíada Vasconcelos Chaves.

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Chaves, H.V., do Val, D.R., Ribeiro, K.A. et al. Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+ channels. Inflamm. Res. 67, 407–422 (2018). https://doi.org/10.1007/s00011-018-1133-z

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