tDCS and exercise improve anxiety-like behavior and locomotion in chronic pain rats via modulation of neurotrophins and inflammatory mediators

• Published in: Behavioural brain research 2021-04, Vol.404, p.113173-113173, Article 113173
• Main Authors: Lopes, Bettega Costa, Medeiros, Liciane Fernandes, Stein, Dirson João, Cioato, Stefania Giotti, de Souza, Vanessa Silva, Medeiros, Helouise Richardt, Sanches, Paulo Roberto Stefani, Fregni, Felipe, Caumo, Wolnei, Torres, Iraci L.S.
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Anxiety - therapy; Biomarkers; Brain-Derived Neurotrophic Factor - analysis; Chronic Pain - therapy; Combined Modality Therapy; Deltaproteobacteria - chemistry; Disease Models, Animal; Elevated Plus Maze Test; Exercise; Interleukin-10 - analysis; Locomotion; Male; Pain; Physical Conditioning, Animal - methods; Physical Conditioning, Animal - psychology; Rats; Rats, Wistar; tDCS; Transcranial Direct Current Stimulation - methods; Transcranial Direct Current Stimulation - psychology; Tumor Necrosis Factor-alpha - analysis
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2021.113173

•Neuropathic pain triggered anxiogenic-like behavior in rats.•There was a synergic anxiolytic effect of the combination between tDCS and exercise.•Repeated bimodal tDCS was effective in relieving the anxiety-like behavior.•Eight sessions of exercise were able to relief the anxiety-like behavior.•Peripheral and central neuroimmunomodulatory effects of exercise and/or tDCS. Anxiety disorders cause distress and are commonly found to be comorbid with chronic pain. Both are difficult-to-treat conditions for which alternative treatment options are being pursued. This study aimed to evaluate the effects of transcranial direct current stimulation (tDCS), treadmill exercise, or both, on anxiety-like behavior and associated growth factors and inflammatory markers in the hippocampus and sciatic nerve of rats with neuropathic pain. Male Wistar rats (n = 216) were subjected to sham-surgery or sciatic nerve constriction for pain induction. Fourteen days following neuropathic pain establishment, either bimodal tDCS, treadmill exercise, or a combination of both was used for 20 min a day for 8 consecutive days. The elevated plus-maze test was used to assess anxiety-like behavior and locomotor activity during the early (24 h) or late (7 days) phase after the end of treatment. BDNF, TNF-ɑ, and IL-10 levels in the hippocampus, and BDNF, NGF, and IL-10 levels in the sciatic nerve were assessed 48 h or 7 days after the end of treatment. Rats from the pain groups developed an anxiety-like state. Both tDCS and treadmill exercise provided ethological and neurochemical alterations induced by pain in the early and/or late phase, and a modest synergic effect between tDCS and exercise was observed. These results indicate that non-invasive neuromodulatory approaches can attenuate both anxiety-like status and locomotor activity and alter the biochemical profile in the hippocampus and sciatic nerve of rats with neuropathic pain and that combined interventions may be considered as a treatment option.