Analgesia induced by preemptive tDCS in a rat model of incisional pain: peripheral and central mechanisms
Dirson João Stein (1,2,3); Mayra Zancanaro (1,2,3); José Antônio Fagundes Assumpção (1,2,3); Bettega Costa Lopes (1,3,4); Felipe Fregni (5); Wolnei Caumo (2); Iraci Lucena da Silva Torres (1,2,3,4)
1Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-Clínicas - Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil
2Programa de Pós-Graduação em Medicina: Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
3Unidade de Experimentação Animal, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil
4Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
5Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard University, Boston, MA, United States
OBJECTIVE: To investigate the effects of preemptive tDCS over nociceptive/inflammatory parameters in male Wistar rats subjected to a model of incisional pain.
METHODS: 40 adult male Wistar rats, divided into five groups: control, sham surgery, surgery, sham tDCS+surgery, tDCS+surgery. Active (0.5mA) bimodal or sham tDCS were applied before the incisional pain model (8 days/20 min/day). Mechanical allodynia was assessed by von Frey test before and after surgery. Cytokines and BDNF were evaluated in the cerebral cortex, hippocampus, brainstem and spinal cord. On the incision site, the activity of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) and the presence of edema, suppuration, hyperemia, angiogenesis, and infiltration of neutrophils, lymphocytes, plasmocytes, and macrophages were evaluated. Data analyzed by GEE/Bonferroni, one-way ANOVA/SNK, and Kruskal-Wallis (mean±SEM/median, P<0.05). Study approved by CEUA/HCPA (#2016.0295).
RESULTS: Immediately and 30 min after surgery, tDCS partially reversed mechanical allodynia, and totally reversed from 48h up to 72h after surgery. tDCS reduced the levels of hippocampal IL-1β e IL-10, increased levels of brainstem IL-1β, TNF-ɑ and BDNF, and reduced levels of spinal cord IL-10, compared to no treated rats. tDCS reduced the activity of MPO and NAGase, the presence of edema, suppuration and number of neutrophils and macrophages on the lesion site.
CONCLUSIONS: The use of preemptive tDCS showed to be effective in controlling post-surgical pain, modulating central cytokine and BDNF levels, contributing to tissue repair, preventing chronic inflammation and the emergence of fibrosis. The use of preemptive tDCS may reduce the use of post-surgical drugs, reduce costs and improve post-surgical recovery.
KEYWORDS: nociception; postsurgical pain; neuromodulation, Wistar rats.
ACKNOWLEDGMENTS: We would like to express our very great appreciation for the Department of Biomedical Engeneering of Hospital de Clínicas de Porto Alegre, for developing the tDCS device and for their technical assistance during the experiments.
FUNDING/FINANCIAL SUPPORT: CAPES, CNPq, FIPE-HCPA 160295, FINEP/2013, FAPERGS.