Relevance of Mitochondrial Dysfunction in the Reserpine-Induced Experimental Fibromyalgia Model
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Relevance of Mitochondrial Dysfunction in the Reserpine-Induced Experimental Fibromyalgia Model Evelyne da Silva Brum 1 & Maria Fernanda Pessano Fialho 1 & Susana Paula Moreira Fischer 1 & Diane Duarte Hartmann 1 & Débora Farina Gonçalves 1 & Rahisa Scussel 2 & Ricardo Andrez Machado-de-Ávila 2 & Cristiane Lenz Dalla Corte 1,3 & Félix Alexandre Antunes Soares 1,3 & Sara Marchesan Oliveira 1,3 Received: 6 February 2020 / Accepted: 22 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Fibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitochondrial modulators. Reserpine (1 mg/kg) was subcutaneously injected once daily for three consecutive days in male Swiss mice. We carried out analyses of reserpine-induced FM-related symptoms, and their modulation by using mitochondrial insult on ATP synthesis (oligomycin; 1 mg/kg, intraperitoneally) or mitochondrial protection (coenzyme Q10; 150 mg/kg/5 days, orally). We also evaluated the effect of reserpine on mitochondrial function using high-resolution respirometry and oxidative status. Reserpine caused nociception, loss in muscle strength, and anxiety- and depressive-like behaviours in mice that were consistent with clinical symptoms of FM, without inducing body weight and temperature alterations or motor impairment. Reserpine-induced FM-related symptoms were increased by oligomycin and reduced by coenzyme Q10 treatment. Reserpine caused mitochondrial dysfunction by negatively modulating the electron transport system and mitochondrial respiration (ATP synthesis) mainly in oxidative muscles and the spinal cord. These results support the role of mitochondria in mediating oxidative stress and FM symptoms in this model. In this way, reserpine-inducing mitochondrial dysfunction and increased production of ROI contribute to the development and maintenance of nociceptive, fatigue, and depressive-like behaviours. Keywords Allodynia . Depression . Oligomycin . Coenzyme Q10 . High-resolution respirometry . Oxidative status
Headings • Oligomycin (ATP insult) enhanced reserpine-induced pain and depressive-like behaviours. • Coenzyme Q10 prevented reserpine-induced pain and depressive-like behaviours. • Reserpine reduced electron transport and mitochondrial respiration in the muscles and spinal cord. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-01996-1) contains supplementary material, which is available to authorized users. * Sara March
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