Inflammation Research

, Volume 67, Issue 5, pp 407–422 | Cite as

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

  • Hellíada Vasconcelos Chaves
  • Danielle Rocha do Val
  • Kátia Alves Ribeiro
  • Jonas Cavalcante Lemos
  • Ricardo Basto Souza
  • Francisco Isaac Fernandes Gomes
  • Rodrigo Maranguape Silva da Cunha
  • Vicente de Paulo Teixeira Pinto
  • Gerardo Cristino Filho
  • Marcellus Henrique Loiola Ponte de Souza
  • Mirna Marques Bezerra
  • Gerly Anne de Castro Brito
Original Research Paper
  • 87 Downloads

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.

Keywords

Inflammation IL-1β Heme oxygenase-1 Temporomandibular joint TNF-α. 

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

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests regarding the publication of this article.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Hellíada Vasconcelos Chaves
    • 1
  • Danielle Rocha do Val
    • 2
  • Kátia Alves Ribeiro
    • 3
  • Jonas Cavalcante Lemos
    • 4
  • Ricardo Basto Souza
    • 3
  • Francisco Isaac Fernandes Gomes
    • 1
  • Rodrigo Maranguape Silva da Cunha
    • 5
  • Vicente de Paulo Teixeira Pinto
    • 4
  • Gerardo Cristino Filho
    • 4
  • Marcellus Henrique Loiola Ponte de Souza
    • 6
  • Mirna Marques Bezerra
    • 4
  • Gerly Anne de Castro Brito
    • 6
  1. 1.Faculty of Dentistry of SobralFederal University of CearáSobralBrazil
  2. 2.Federal University of PernambucoNorth Eastern Biotechnology NetworkRecifeBrazil
  3. 3.Master of Biotechnology Degree ProgrammeFederal University of CearáSobralBrazil
  4. 4.Faculty of MedicineFederal University of CearáSobralBrazil
  5. 5.Biotechnology Research GroupState University of Acaraú ValleySobralBrazil
  6. 6.Department of Physiology and Pharmacology, Faculty of MedicineFederal University of CearáFortalezaBrazil

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