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Transcranial Direct Current Stimulation (tDCS) Induces Analgesia in Rats with Neuropathic Pain and Alcohol Abstinence

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Abstract

Neuromodulatory techniques have been studied to treat drug addiction or compulsive eating as well as different chronic pain conditions, such as neuropathic and inflammatory pain in the clinical and preclinical settings. In this study, we aimed to investigate the effect of transcranial direct current stimulation (tDCS) on the association of alcohol withdrawal with neuropathic pain based on nociceptive and neurochemical parameters in rats. Thirty-six adult male Wistar rats were randomized into five groups: control, neuropathic pain, neuropathic pain + tDCS, neuropathic pain + alcohol, and neuropathic pain + alcohol + tDCS. The neuropathic pain model was induced by chronic constriction injury (CCI) to the sciatic nerve. Rats were then exposed to alcohol (20%) by oral gavage administration for 15 days (beginning 24 h after CCI). tDCS was started on the 17th day after surgery and lasted for 8 consecutive days. The nociceptive test (hot plate) was performed at baseline, 16 days after CCI, and immediately and 24 h after the last session of tDCS. Rats were killed by decapitation, and structures were removed and frozen for biochemical analysis (nerve growth factor and interleukin (IL-1α, IL-1β, and IL-10 measurements). Neuropathy-induced thermal hyperalgesia was reversed by tDCS, an effect that was delayed by alcohol abstinence. In addition, tDCS treatment induced modulation of central levels of IL-1α, IL-1ß, and IL-10 and neurotrophic growth factor. We cannot rule out that the antinociceptive effect of tDCS could be related to increased central levels of IL-1α and IL-10. Therefore, tDCS may be a promising non-pharmacological therapeutic approach for chronic pain treatment.

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Acknowledgements

The authors thank the Biomedical Engineering group from the Hospital de Clínicas de Porto Alegre (HCPA) for the development of the tDCS equipment used in this study.

Funding

This work was supported by the following Brazilian funding agencies: Brazilian Federal Agency for Support and Evaluation of Graduate Education—CAPES/MD-PhD (D.S. Santos, B.C. Lopes, L.S. Santos); National Council for Scientific and Technological Development—CNPq (Dr. I.L.S. Torres, Dr. W. Caumo); Graduate Research Group of the Hospital de Clínicas de Porto Alegre—GPPG (I.L.S. Torres, Grant No.: 15–0501) MCT/FINEP—COENG/2013; and the Support Program for Emerging Nuclei PRONEM (Paulo Roberto Sanches, Grant No. 16/2551-0000249-5).

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Authors and Affiliations

  1. Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-Clínicas, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Daniela Silva Santos, Bettega Costa Lopes, Liciane Fernandes Medeiros, José Antônio Fagundes Assumpção, Andressa de Souza, Artur Alban Salvi, Lisiane Santos da Silva & Iraci L. S. Torres

  2. Programa de Pós-Graduação em Medicina: Ciências Médicas, Faculdade de Medicina, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil

    Daniela Silva Santos, José Antônio Fagundes Assumpção, Lisiane Santos da Silva, Wolnei Caumo & Iraci L. S. Torres

  3. Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Bettega Costa Lopes & Iraci L. S. Torres

  4. Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil

    Liciane Fernandes Medeiros & Iraci L. S. Torres

  5. Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard University, Boston, MA, USA

    Felipe Fregni

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

    Liciane Fernandes Medeiros & Andressa de Souza

  7. Unidade de Experimentação Animal, Grupo de Pesquisa e Pós-Graduação, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Daniela Silva Santos, Bettega Costa Lopes, José Antônio Fagundes Assumpção, Artur Alban Salvi, Lisiane Santos da Silva & Iraci L. S. Torres

  8. Laboratory of Pain Pharmacology and Neuromodulation: Pre-clinical Research, Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, 90035-007, Brazil

    Iraci L. S. Torres

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  1. Daniela Silva Santos
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Contributions

DSS and ILST were responsible for the study concept and design. DSS, BCL, LSS, AS, and JA contributed to the acquisition of data. DSS, LFM, JA, and ILST were responsible for data analysis. DSS, LFM, FF, WC, and ILST drafted the manuscript. All authors revised and edited the manuscript as well as approved the final version.

Corresponding author

Correspondence to Iraci L. S. Torres.

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Conflict of interest

All authors declares that they have no conflict of interest. 

Ethical Approval

All experiments and procedures were approved by the Institutional Animal Care and Use Committee of the Hospital de Clínicas de Porto Alegre/HCPA (GPPG-HCPA protocol no. 15.0501). The experimental protocol complied with the ethical and methodological standards of the ARRIVE guidelines (Kilkenny et al. 2013).

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Santos, D.S., Lopes, B.C., Medeiros, L.F. et al. Transcranial Direct Current Stimulation (tDCS) Induces Analgesia in Rats with Neuropathic Pain and Alcohol Abstinence. Neurochem Res 45, 2653–2663 (2020). https://doi.org/10.1007/s11064-020-03116-w

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  • DOI: https://doi.org/10.1007/s11064-020-03116-w

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