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
Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, SC, Brazil.
Coastal Health Institute, Jacksonville, FL, United States.
Front Integr Neurosci. 2023 Oct 12;17:1242278. doi: 10.3389/fnint.2023.1242278. eCollection 2023.
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 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days.
pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). 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.
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.
本研究评估了经皮迷走神经电刺激（pVNS）联合体育锻炼（即游泳）对周围炎症小鼠的抗痛觉过敏和抗炎作用。
通过足底注射弗氏完全佐剂（CFA）诱导疼痛模型。64只雄性瑞士小鼠（35 - 40克）接受足底注射CFA，并进行行为测试，即机械性痛觉过敏、水肿和爪部温度测试。此外，通过酶联免疫吸附测定法测定细胞因子水平，特别是白细胞介素-6（IL-6）和白细胞介素-10（IL-10）。小鼠连续四天单独进行30分钟游泳锻炼，或与左耳不同时间方案（10、20或30分钟）的随机频率刺激联合进行。
20分钟的pVNS在CFA注射后24小时内将抗痛觉过敏作用延长至2小时。30分钟的pVNS在CFA注射后96小时内将抗痛觉过敏作用延长至7小时。然而，在分析的两个时间点（24小时和96小时），它并未改变水肿或温度。此外，pVNS加游泳锻炼的联合方式而非单独的游泳锻炼降低了爪部和脊髓中的IL-6水平以及脊髓中的IL-10水平。
pVNS增强了游泳诱导的镇痛作用，这可能至少部分是由外周（爪部）和中枢神经系统（脊髓）中炎症细胞因子的调节介导的。因此，这些疗法的联合可能作为持续性炎症性疼痛的重要辅助治疗方法。
