AUTHOR=Dutra Aline Raulino , Salm Daiana Cristina , da Silva Rafaela Hardt , Tanaka Fernanda , Lutdke Daniela Dero , de Oliveira Bruna Hoffmann , Lampert Rose , Bittencourt Edsel B. , Bianco Gianluca , Gadotti Vinícius M. , Reed William R. , Mack Josiel Mileno , Bobinski Franciane , Moré Ari O. O. , Martins Daniel Fernandes 

TITLE=Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation

JOURNAL=Frontiers in Integrative Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/integrative-neuroscience/articles/10.3389/fnint.2023.1242278

DOI=10.3389/fnint.2023.1242278

ISSN=1662-5145

ABSTRACT=This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 minutes alone or associated with different time protocols (10, 20, or 30 minutes) of stimulation in the left ear with random frequency during four consecutive days. pVNS for 20 minutes prolonged the antihyperalgesic effect for up to 2 hours, twenty-four hours after CFA injection. pVNS for 30 minutes prolonged the antihyperalgesic effect for up to 7 hours, ninety-six hours after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 hours and 96 hours). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. In conclusion, pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.