Abstract
The present study aimed to evaluate the possible peripheral H2O2-induced antinociception and determine the involvement of opioidergic, cannabinoidergic and nitrergic systems, besides potassium channels in its antinociceptive effect. Prostaglandin E2 was used to induce hyperalgesia in male Swiss mice using the mechanical paw pressure test. H2O2 (0.1, 0.2, 0.3 µg/paw) promoted a dose-dependent antinociceptive effect that was not observed in contralateral paw. Female mice also showed antinociception in the model. The partial H2O2-induced antinociception was potentiated by the inhibitor of catalase enzyme, aminotriazole (40, 60, 80 µg/paw). The antinociception was not reversed by opioid and cannabinoid receptor antagonists naloxone, AM 251 and AM 630. The involvement of nitric oxide (NO) was observed by the reversal of H2O2-induced antinociception using the non-selective inhibitor of nitric oxide synthases L-NOarg and by inhibition of iNOS (L-NIL), eNOS (L-NIO) and nNOS (L-NPA). ODQ, a cGMP-forming enzyme selective inhibitor, also reversed the antinociception. The blockers of potassium channels voltage-gated (TEA), ATP-sensitive (glibenclamide), large (paxillin) and small (dequalinium) conductance calcium-activated were able to revert H2O2 antinociception. Our data suggest that H2O2 induced a peripheral antinociception in mice and the NO pathway and potassium channels (voltage-gated, ATP-sensitive, calcium-activated) are involved in this mechanism. However, the role of the opioid and cannabinoid systems was not evidenced.
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Data availability
The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Federal University of Minas Gerais.
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Acknowledgements
This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Pesquisa) and FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais).
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Conceptualization: IDGD
Data curation: WCPB, BFGP, RCMF
Formal analysis: TLR, ACP, RCMF, IDGD
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Methodology: WCPB, BFGP
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Barra, W., Queiroz, B., Perez, A. et al. Study on peripheral antinociception induced by hydrogen peroxide (H2O2): characterization and mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03087-7
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DOI: https://doi.org/10.1007/s00210-024-03087-7