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Effect of m-Trifluoromethyl-diphenyl diselenide on the Pain–Depression Dyad Induced by Reserpine: Insights on Oxidative Stress, Apoptotic, and Glucocorticoid Receptor Modulation

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Abstract

Chronic pain and depression often coexist sharing common pathological mechanisms, and available analgesics and antidepressants have demonstrated limited clinical efficacy. Evidence has demonstrated that neuronal oxidative stress, apoptosis, and also glucocorticoid receptor dysregulation facilitate the occurrence and development of both chronic pain and depression. This study evaluated the effect of the organoselenium compound m-trifluoromethyl-diphenyl diselenide [(m–CF3–PhSe)2] in the pain–depression comorbidity induced by reserpine. Mice were treated with reserpine 0.5 mg/kg for 3 days (intraperitoneal, once a day), and in the next 2 days, they were treated with (m–CF3–PhSe)2 10 mg/kg (intragastric, once a day). Thirty minutes after the last administration of (m–CF3–PhSe)2, mice were subjected to the behavioral testing. (m–CF3–PhSe)2 treatment reverted the reserpine-increased thermal hyperalgesia and depressive-like behavior observed in the hot-plate test and forced swimming test, respectively. Reserpine provoked a decrease of crossings and rearings in the open-field test, while (m–CF3–PhSe)2 presented a tendency to normalize these parameters. Reserpine and/or (m–CF3–PhSe)2 treatments did not alter the locomotor activity of mice observed in the rota-rod test. These effects could be related to modulation of oxidative stress, apoptotic pathway, and glucocorticoid receptors, once (m–CF3–PhSe)2 normalized thiobarbituric acid reactive substances and 4-hydroxynonenal modified protein levels, markers of lipoperoxidation, poly(ADP-ribose) polymerase cleaved/total ratio, and glucocorticoid receptor levels increased by reserpine in the hippocampus. Considering that pain–depression dyad is a complex state of difficult treatment, this organoselenium compound could raise as an interesting alternative to treat pain–depression condition.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Acknowledgements

We acknowledge Universidade Federal de Pelotas (UFPel), Universidade Federal de Santa Maria (UFSM), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROAP), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 420386/2018-1 and 438384/2018-0) for the financial support. C.W.N. is recipient of CNPq fellowship.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/PROAP), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 420386/2018–1 and 438384/2018–0).

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  1. Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Center for Chemical, Pharmaceutical and Food Sciences (CCQFA), Federal University of Pelotas (UFPel), Pelotas, RS, 96010-900, Brazil

    Cleisson Schossler Garcia, Pabliane Rodrigues Garcia, Carlos Natã da Silva Espíndola, Gustavo D’Avila Nunes, Cristiani Folharini Bortolatto & César Augusto Brüning

  2. Laboratory of Synthesis, Reactivity and Pharmacological and Toxicological Evaluation of Organochalcogens, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil

    Natália Silva Jardim & Sabrina Grendene Müller

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Conceptualization: César Augusto Brüning, Cristiani Folharini Bortolatto and Cleisson Schossler Garcia; Methodology: César Augusto Brüning, Cleisson Schossler Garcia, Pabliane Rodrigues Garcia, Carlos Natã da Silva Espíndola; Gustavo D’Avila Nunes, Natália Silva Jardim and Sabrina Grendene Müller; Formal analysis and investigation: César Augusto Brüning, Cleisson Schossler Garcia, Pabliane Rodrigues Garcia, Carlos Natã da Silva Espíndola; Gustavo D’Avila Nunes, Natália Silva Jardim and Sabrina Grendene Müller; Writing—original draft preparation: Cleisson Schossler Garcia, Pabliane Rodrigues Garcia, Carlos Natã da Silva Espíndola and Gustavo D’Avila Nunes; Writing—review and editing: César Augusto Brüning and Cristiani Folharini Bortolatto; Funding acquisition: César Augusto Brüning and Cristiani Folharini Bortolatto; Resources: César Augusto Brüning and Cristiani Folharini Bortolatto; Supervision: César Augusto Brüning and Cristiani Folharini Bortolatto.

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Correspondence to Cristiani Folharini Bortolatto or César Augusto Brüning.

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The experiments with animals were carried out in accordance with the Research Ethics Committee of the Federal University of Santa Maria (approval number of the ethics committee: 4664250915), affiliated to the National Council for Animal Experimentation Control (CONCEA), in accordance with the Guide from the National Institutes of Health for the care and use of laboratory animals (NIH Publications No. 8023, revised in 1978).

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Schossler Garcia, C., Garcia, P.R., da Silva Espíndola, C.N. et al. Effect of m-Trifluoromethyl-diphenyl diselenide on the Pain–Depression Dyad Induced by Reserpine: Insights on Oxidative Stress, Apoptotic, and Glucocorticoid Receptor Modulation. Mol Neurobiol 58, 5078–5089 (2021). https://doi.org/10.1007/s12035-021-02483-x

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